Biomedical subjects

P W Peake

Publications and source records attributed to P W Peake.

At least 19 recordsLinked to original sources

PubMed1997

Detection and quantification of the control proteins of the alternative pathway of complement in 3T3-L1 adipocytes.

The complement peptide C3a desarg is identical to acylation-stimulating protein (ASP), a human plasma protein that potently stimulates adipocyte triacylglycerol synthesis and glucose transport. Both human and murine adipocytes express mRNA and/or protein for the complement components C3 and factors B and D (adipsin) required to generate ASP. However, the regulatory mechanisms controlling this process are unknown. We have established a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique to demonstrate the presence in mouse 3T3-L1 adipocytes of mRNA for all components of the alternative pathway, including the control proteins factors I and H, CR1 and properdin. On differentiation, mRNA for C3 (fivefold) and factor D (> 50-fold) increased, whereas stimulation with tumour necrosis factor (TNF)-alpha and interleukin (IL) 1 beta led to eightfold increases in factor B mRNA. Metabolic labelling followed by immunoprecipitation showed that factor B protein is normally present in small quantities, and is greatly increased by cytokine stimulation. The larger quantities of C3 and H proteins present were little affected, whereas levels of C3a increased on cytokine stimulation. These results suggest that the rate-limiting step in the cytokine-induced production of ASP in adipocytes is factor B synthesis.

3T3 Cells↗

PubMed1996

The metabolism of C9 in normal subjects and in patients with autoimmune disease.

The metabolism of the ninth component of complement (C9) was studied in eight healthy subjects and nine patients with autoimmune disease, including seven with systemic lupus erythematosus (SLE) and one each with mesangial IgA nephropathy and mixed essential cryoglobulinaemia. In normal subjects the metabolic parameters(mean +/- s.d.) were : fractional catabolic rate (FCR): 2.92 +/- 0.36%/h, plasma half-life (T1/2): 42.5 +/- 6.7 h, and extravascular/intravascular distribution ratio (EV/IV): 0.56 +/- 0.12. In patients the FCR was 3.38 +/- 0.70%/h, the T1/2 was 37.6 +/- 10.2 h, and the EV/IV was 0.55 +/- 0.19. Patients with reduced total serum haemolytic activity (i.e. CH50 <68% of normal human serum (NHS), N=7) had significantly higher FCR (3.57 +/- 0.67%/h) and shorter T1/2(33.5 +/- 6.8 h) than the control group (both P<0.05). The plasma concentration of the terminal complement complex (i.e. soluble TCC or SC5b-9) was higher in patients (median (range): 515 (300-1879 micrograms/l) than in normal subjects (313 (229-402 micrograms/liters): P<0.01) and showed a positive correlation with the FCR of C9 (r=0.61, P<0.01). Plasma C9 production rate was also greater in patients (0-11 +/- 0-05 mg/kg per h) compared with control subjects (0-07 +/- 0.03 mg/kg per h, P<0.05), and was associated with a higher C9 concentration in patients' sera (76 +/- 13 mg/l versus 61 +/- 14 mg/l, P<0.05). These results demonstrate that C9 is rapidly metabolized in normal humans and that hypercatabolism occurs in patients with autoimmune disease and complement activation. This was despite the presence of normal or elevated serum C9 levels and normal compartmental distribution.

Adult↗

PubMed1996

The behaviour of human vitronectin in vivo: effects of complement activation, conformation and phosphorylation.

We examined the behaviour in vivo of native, specifically phosphorylated, and multimeric vitronectin to determine the effects of these modifications on its turnover, distribution and molecular behaviour. In normal rabbits, the plasma half-life (T1/2) of antigenically detected vitronectin was 8.00 +/- 1.26 h (mean +/- s.d.), with a fractional catabolic rate (FCR) of 18.77 +/- 1.57%/h and extravascular/intravascular ratio (EV/IV) of 1.00 (0.48-1.60, median and range). For vitronectin selectively phosphorylated by protein kinase A, T1/2 was 8.87 +/- 0.48 h, with a significantly smaller FCR of 10.85 +/- 0.71%/h (P < 0.005) and an EV/IV of 0.28 (0.15-0.36) (P < 0.05 compared with antigenically detected vitronectin). In vitro, phosphorylation had no effect on the affinity of vitronectin for heparin-Sepharose, while complement activation with cobra venom factor (CVF) led to a two-fold enrichment of 32P-vitronectin within the SC5b-9 complex. In vivo CVF caused a rapid decrease in the circulating levels of 32P-vitronectin and was accompanied by the prompt appearance of a high mol. wt species consistent with SC5b-9. Despite specific incorporation of 32P-vitronectin into SC5b-9, both forms of the molecule had similar inhibitory effects on C9-mediated haemolysis of EAC1-7 cells. Urea-activated vitronectin was rapidly cleared from circulation with less than 15% remaining after 1 h while protein-bound label accumulated in the spleen, lung and liver. These results demonstrate that vitronectin is a rapidly metabolized protein whose in vivo behaviour is markedly altered when phosphorylated or activated to form multimers and SC5b-9.

Animals↗

PubMed1995

The kinetics and distribution of C9 and SC5b-9 in vivo: effects of complement activation.

Many diseases associated with complement activation are characterized by tissue deposition of components of the terminal complement complex (TCC). The ninth component of complement (C9) plays an important role in the cytolytic effects, and may contribute to the non-lethal cell-regulating functions of the TCC. In this study we examined the behaviour of radiolabelled human C9 and its soluble complexed form SC5b-9 in vivo in order to determine the effects of complement activation on its turnover, distribution and molecular size. In normal rabbits the metabolic parameters of 125I-C9 (median and range) were: plasma half-life (t1/2) 25.9 (20.6-29.5) h, fractional catabolic rate (FCR) 5.7 (5.3-7.0)%/h, and extravascular/intravascular ratio (EV/IV) 0.7 (0.6-1.1). The distribution of radiolabelled C9 amongst body tissues was similar to that observed for rabbit serum albumin (RSA). Activation of the complement cascade with i.v. injection of cobra venom factor (CVF) resulted in rapid disappearance of C9 from the plasma and accumulation of protein-bound radiolabeled in the spleen (exceeding the plasma concentration) and the liver. RSA metabolism and distribution were unaffected by CVF. Fine performance liquid chromatography (FPLC) gel filtration of plasma samples suggested that monomeric C9 was the only major radiolabelled protein present during normal turnovers, whereas CVF administration was accompanied by the prompt appearance of a high mol. wt species consistent in size with SC5b-9. When injected directly, 125I-SC5b-9 disappeared rapidly from the plasma, falling by 50% in 0.7 (0.6-0.8) h, and less than 15% remaining after 4 h with accumulation of protein-bound label in the spleen and liver. These results demonstrate the complexity of C9 metabolism during complement activation.

Animals↗

PubMed1994

Identification of a Mycobacterium leprae-specific T cell epitope on the 70 kDa heat shock protein.

A major antigen of the leprosy bacillus, Mycobacterium leprae, is the 70 kDa heat shock protein (Hsp70), which has significant sequence homology with Hsp70 from other mycobacterial species as well as Hsp70 from eukaryotes. A unique region of 70 amino acids at the C-terminus of the M. leprae Hsp70 has been previously identified. This study investigated whether mice immunized with the C-terminal fragment of M. leprae Hsp70 recognize T cell epitopes in this species-specific portion of the molecule. Murine lymphoproliferative responses to overlapping peptides spanning the C-terminal 70 amino acids were restricted to mice of an H-2b haplotype and identified the presence of a determinant in sequence 567-591. Lymph node cells from mice immunized with this peptide recognized both the C-terminal fragment and the whole Hsp70 molecule. Moreover, mice immunized with the same peptide responded to the whole Hsp70 molecule in a delayed-type hypersensitivity reaction. The significance of M. leprae-specific T cell epitopes in the host response to mycobacterial infection is discussed.

Amino Acid Sequence↗

PubMed1994

T-cell determinants and antibody binding sites on the major mycobacterial secretory protein MPB59 of Mycobacterium bovis.

Among the first proteins encountered by the host immune system upon infection or vaccination with mycobacteria are those secreted by the bacillus during growth. The antigen 85 complex of Mycobacterium bovis bacillus Calmette-Gúerin (BCG) is composed of three closely related members. The mature 85B protein of M. bovis (MPB59) has a high degree of amino acid identity with the M. bovis 85A protein (76%) and the Mycobacterium tuberculosis 85B (99%) and 85A (76%) proteins. We have examined the regions of MPB59 which stimulate human T- and B-cell responses by use of a set of 28 synthetic peptides, 20 amino acids (aa) in length and overlapping by 10 aa. Initial proliferative assays with recombinant MPB59 demonstrated that peripheral blood mononuclear cells from 95% of BCG vaccinees and 52% of tuberculosis patients responded to the whole mature protein. Peripheral blood mononuclear cells from MPB59 responders, but not nonresponders, were stimulated by peptides in a dose-dependent fashion. Five peptides were reactive in more than half of the MPB59 responders. The T-cell-reactive regions were essentially identical in the M. bovis and M. tuberculosis 85B proteins. Subjects with a variety of HLA-DR phenotypes responded to a number of these peptides. The dominant T-cell-reactive regions were distinct from the peptides recognized by sera from tuberculosis patients (aa 71 to 100) and the murine monoclonal antibody HYT27 (aa 61 to 90). The region reactive with antibodies overlapped part of the MPB59 sequence recently shown to participate in the binding of MPB59 to fibronectin.

Amino Acid Sequence↗

PubMed1993

Analysis of B-cell epitopes in the variable C-terminal region of the Mycobacterium leprae 70-kilodalton heat shock protein.

The C-terminal region of the Mycobacterium leprae 70-kDa heat-shock protein is the major target for the humoral immune response to this protein and contains M. leprae-specific sequences. To examine B-cell responses to this region more closely, we constructed and expressed a recombinant fragment of the M. leprae P70 gene that encodes the C-terminal 142 residues (C-142) and synthesized a series of 10 overlapping peptides to encompass this region. The affinities of three monoclonal antibodies (MAbs) reactive with this region of P70 were measured, and the binding site of the highest-affinity MAb was determined to lie between residues 498 and 515. This reactivity was confirmed by a fluid-phase inhibition enzyme-linked immunosorbent assay. By contrast, sera from leprosy patients which were strongly reactive with the C-142 fragment failed to bind directly to the conjugated or unconjugated peptides. To determine whether the M. leprae-specific C-terminal 70 residues could stimulate B-cell responses, the reactivity of hyperimmune anti-M. leprae P70 antisera with the peptides was examined. Rabbit polyclonal anti-M. leprae P70 antisera recognized epitopes between residues 498 and 515 and in the M. leprae-specific region between residues 567 and 591. The latter, in turn, when coupled to ovalbumin, was able to generate a strong anti-P70 response specific for mycobacterial, but not human, HSP70. Three strains of mice immunized with either C-142 or P70 recognized epitopes in the region between residues 487 and 532, but the response varied with the strain and immunogen. These data demonstrate that two regions in the C-terminal portion of M. leprae P70 contain linear B-cell epitopes recognized by MAbs or hyperimmune serum. Sera from leprosy patients, however, react predominantly with conformational determinants in the immunodominant C-terminal part of the protein.

Amino Acid Sequence↗

PubMed1992

Emergency management of near drowning.

The immediate and continuing management of an 'immersion victim' is described in this article. Proper assessment of the patient and the details of cardiopulmonary resuscitation are revised.

Adolescent↗

PubMed1991

The inhibitory effect of rosmarinic acid on complement involves the C5 convertase.

Rosmarinic acid (RA), a naturally occurring extract from Melissa officinalis, inhibits several complement-dependent inflammatory processes and may have potential as a therapeutic agent for the control of complement activation in disease. Rosmarinic acid has been reported to have effects on both the classical pathway C3-convertase and on the cobra venom factor-induced, alternative pathway convertase. In order to define the mechanism of inhibition, the effect of RA on classical and alternative pathway lysis, C1q binding, the classical pathway convertase, the alternative pathway convertase, membrane attack pathway lysis and the generation of fragments of C3 and C5 during activation, was tested in vitro. The results showed that RA inhibited lysis by the classical pathway more than by the alternative pathway. This effect was dose-dependent with maximum inhibition of classical pathway lysis observed at 2.6 mmoles of RA. There was little effect on C1q binding or on the classical and alternative pathway convertases. However, there was highly significant inhibition of lysis of pre-formed EA43b cells by dilutions of human or rabbit serum in the presence of RA (1 mM); this was accompanied by inhibition of C5a generation. We conclude that the inhibitory effect of RA involves the C5 convertase. Such inhibition could be advantageous to the host in disorders where the terminal attack sequence plays a role in pathogenesis.

Animals↗

PubMed1991

Post-streptococcal glomerulonephritis: studies on the interaction between nephritis strain-associated protein (NSAP), complement and the glomerulus.

Nephritis strain-associated protein (NSAP), a streptokinase produced by strains of streptococci isolated from patients with acute glomerulonephritis, is believed to be a specific antigen which participates in the production of glomerular injury. In order to investigate the mechanisms by which NSAP induces damage we have examined its potential to activate complement in vitro and to bind to isolated human glomeruli. NSAP, both alone and in combination with specific antibody, caused depletion of complement in normal human serum as measured by total haemolytic complement activity and generation of the complement breakdown products. C3a and C4a. Furthermore, Scatchard analysis showed that NSAP bound tightly to human glomeruli (Ka of 400 +/- 240 x 10(6) M) when compared to non-nephritic streptokinase (Ka of 7.3 +/- 4.1 x 10(6) M) and fully cationized human serum albumin (Ka of 0.6 +/- 0.04 x 10(6) M). These findings are consistent with the hypothesis that the deposition of streptococcal antigens within the glomerulus may precede the fixation of complement and specific antibody.

Bacterial Proteins↗

PubMed1991

Activation of rabbit C3: studies of the generation of cleavage products in vitro and of their metabolism in vivo.

The cleavage of purified, functionally active rabbit C3 by cobra venom factor and trypsin was analysed by reducing and non-reducing sodium dodecyl sulphate electrophoresis and autoradiography. The specific aim of the study was to compare these reactions to those that occur with human C3. Analysis showed that the pattern of breakdown was very similar to that for the human protein: while the beta-chain remained intact, there was step-wise degradation of the alpha-chain to form C3a, C3b, iC3b and C3c, all of which could be identified by gel analysis. The metabolic behaviour of three of these cleavage products, C3a, C3b and iC3b, was then examined in vivo using dual isotope techniques. Rabbits were studied simultaneously with 131I-C3 and 125I-labelled C3 breakdown products. Analysis of plasma and urine radioactivity for the subsequent 72 h showed that all three breakdown proteins had rapid rates of catabolism in vivo compared to the native molecule. Specifically, 93 and 98% of C3b and iC3b, respectively, were eliminated from the plasma compartment within 10 h of injection. C3a was completely eliminated within 10 h. By comparison, native C3 showed a half-life of 29 +/- 3 h (mean +/- SD) and a fractional catabolic rate of 4.30 +/- 0.75%/h. The data support the use of this species in studies of complement behaviour in models of human immune disease and further clarify the basis for changes in plasma C3 concentration that accompany active immune complex- and antibody-mediated activity, in vivo.

Animals↗

PubMed1990

Angiotensin II receptor regulation in anti-glomerular basement membrane nephritis.

The expression of the glomerular receptor for angiotensin II (Ang II-R) was examined longitudinally following the induction of anti-glomerular basement membrane (GBM) nephritis in the rat. The specific aim of the project was to determine whether immunologically-induced glomerular injury led to significant abnormalities of the relationship between glomerular Ang II-R and its circulating ligand, Ang II. Scatchard analysis was used to measure Ang II-R on purified glomeruli at selected time intervals over two months following a single dose of sheep anti-rat GBM antibody. Corresponding values for plasma Ang II were determined. Receptor density fell to approximately 50% by 16 hours following the injection of antibody (control 96.4 +/- 9.3 x 10(6); nephritic 52.6 +/- 5.6 x 10(6) receptors/glomerulus; P less than 0.001) and there was a corresponding threefold increase in plasma Ang II (control 21.0 +/- 2.5; nephritic 66.6 +/- 20.6 pg/ml; P less than 0.01). However, this reduction in receptor binding could not be explained by the rise in plasma Ang II concentration, as effective blockade of the RAS by enalapril did not alter receptor expression (56.1 +/- 4.6 x 10(6) receptors/glomerulus). Subsequently, a rise in receptor density and a corresponding fall in plasma Ang II were observed: three days after antibody administration, receptor concentration had increased significantly above control values (150.5 +/- 11.9 x 10(6] while plasma Ang II was undetectable (that is, less than 5 pg/ml). Ang II-R remained elevated for the next two weeks but returned to normal four to eight weeks after the administration of nephrotoxic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1990

Studies of the acute phase response in experimental serum sickness.

The acute phase behavior of C-reactive protein (C-RP), the third component of complement (C3) and total haemolytic complement activity was studied during the course of acute serum sickness (ASS) in rabbits. The specific aim was to establish whether the induction protocol caused a significant change in the serum concentration of proteins (such as C3) which could modify the outcome of the disease. ASS was induced by an intravenous (IV) bolus of bovine serum albumin (250 mg/Kg) with or without prior subcutaneous (SC) immunization with 4 mg BSA in complete Freund's adjuvant. Thirty-six animals received a full induction regimen (i.e., both SC and IV BSA). A further six rabbits were given either IV or SC BSA alone, in order to define the basis for acute phase changes observed when both injections were given. Twelve animals received a standard acute phase stimulus with intramuscular (IM) turpentine--2 or 3 ml--as a comparison to the response observed in the experimental animals. Nine, 14 and 24 animals showed a rise in C-RP (i.e., five-fold increase), C3 and haemolytic activity (greater than 25% increase) respectively after a full induction protocol. Eight, nine and five animals showed a comparable rise with IM turpentine. Studies with IV or SC BSA alone showed that the latter was predominantly responsible for the rise in C-RP and haemolytic activity. Specifically, five and four animals respectively showed a significant rise in these two parameters. Three animals showed a rise in C-RP following IV BSA alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1989

The metabolism of C3 and C4 in patients with immune complexes and normal complement levels.

The metabolism of the complement proteins, C3 and C4 was examined in two groups of patients with a high incidence of detectable immune complexes but normal levels of complement components. The specific aim was to ascertain whether significant ongoing complement activation occurred in these patients. Eleven patients with rheumatoid arthritis (RA), 11 with infection and 11 control subjects were studied. Each received approximately 10 microCi 125l.C4 and 2.5 microCi 131l.C3 by intravenous injection. Analysis of turnover data showed that there was significant hypercatabolism of both C3 and C4 in the two study groups compared to controls. Plasma production of C4 was normal for both groups (despite the presence of C4 null alleles in six out of 11 of the RA group), while C3 production was significantly elevated in both RA and infection (p less than 0.01 and p less than 0.001 respectively). Patients with infection showed a significant increase in extravascular/intravascular distribution of both proteins. The data show that immune complex formation is associated with accelerated turnover of complement proteins, irrespective of co-existing tissue damage or changes in the serum concentration of complement components. The findings suggest that both activation of complement and maintenance or enhancement of protein synthesis are important for the efficient processing of immune complexes in vivo.

Antigen-Antibody Complex↗

PubMed1989

Hypercatabolism of C3 and C4 in active and inactive systemic lupus erythematosus.

The metabolism of the complement proteins C3 and C4 was studied in patients with active and inactive systemic lupus erythematosus (SLE) using highly purified, functionally active preparations. Nine patients with active and eight with inactive SLE were examined and 11 control subjects. There was a significant difference in the level of double stranded DNA antibodies, immune complexes, and serum C4 between the patients with active and inactive disease. Seven of 16 patients had detectable C4 null alleles and four had low serum concentrations of complement inhibitors. Each subject received approximately 370 kBq [125I]C4 and 93 kBq [131I]C3. Both patient groups showed significant C4 hypercatabolism compared with control subjects, but there was no difference between patients with active and inactive disease. The fractional catabolic rate (FCR) of C4 was comparable in subjects with and without detectable C4 null alleles. C4 production rate was significantly lower in patients with active SLE than in control subjects. There was significant C3 hypercatabolism for both patient groups, but C3 production was normal. An inverse correlation was observed between serum concentration and FCR. There was a highly significant correlation between C4 FCR and C3 FCR for control subjects + patients with inactive disease but not for those with active SLE combined with either controls or the inactive group. We conclude that complement hypercatabolism occurs in SLE irrespective of disease activity and that accelerated turnover does not account completely for the low C4 concentration observed in patients with active disease. This low concentration also results from impaired plasma production, which could reflect a high incidence of C4 null alleles or (inhibitory) factors associated with pathological complement activation, or both. Low C4 production could affect generation of the C3 converting enzyme C4b, 2b and thus influence proceeding complement activation.

Alleles↗

PubMed1989

Differences in the metabolism of C4 isotypes in patients with complement activation.

The metabolism of the C4 allotypes C4A3,B1 and C4A3,BO was studied in five healthy control subjects and six patients with active immunological disease (five with systemic lupus erythematosus and one with rheumatoid arthritis). The specific aim was to identify any differences in the metabolism of C4A and C4B gene products that may be linked to their documented functional differences in vitro. The fractional catabolic rate of C4A3,B1 in patients was significantly greater than that of C4A3,BO (3.98 +/- 1.37 versus 3.31 +/- 0.85%/h; mean +/- s.d.; P less than 0.05) but there was no difference in control subjects (1.95 versus 1.99%/h). The extravascular:intravascular (EV:IV) distribution ratio of C4A3,B1 was also greater in both patients (1.19 +/- 0.36 versus 0.97 +/- 0.35; P less than 0.01) and controls (0.43 +/- 0.11 versus 0.31 +/- 0.13; P = 0.01). We conclude that C4B1 was catabolized more rapidly than C4A3 in patients with pathological complement activation but not in control subjects. This difference could reflect the relatively greater extravascular distribution (i.e. EV:IV ratio) of C4B at sites of immune complex deposition or, alternatively, different rates of catabolism of inactive C4 isotypes (iC4b).

Alleles↗

PubMed1989

Does non-enzymatic glycosylation affect complement function in diabetes?

We examined the role of non-enzymatic glycosylation in abnormalities of the complement system commonly found in Type 1 diabetes. Fourteen patients were found to have significantly increased levels of glycosylated C3 (p less than 0.001) and C4 (p less than 0.002) with levels of glycosylated C3 being higher than those of C4 (4.1 +/- 2.5% vs 0.8 +/- 0.8%). This correlated with the finding that in vitro, purified C3 was far more susceptible to this modification than C4. Autoradiography of limited trypsin digests of H3-glycosylated iC3 showed several sites were available for reaction. However, high levels of in vitro glycosylation had no significant effect on the haemolytic activity of C3 and C4, or the binding of iC3 to the CR1 receptor on erythrocytes. Further, IgG was similarly unaffected by non-enzymatic glycosylation in its ability to activate the complement pathway, or when present in an immune complex, to be dissociated from it by complement. We concluded that the immune complex-mediated damage implicated in some complications of Type 1 diabetes is unlikely to derive from any loss of complement function due to non-enzymatic glycosylation.

Antigen-Antibody Complex↗

PubMed1988

Lymphocytotoxic antibodies in systemic lupus erythematosus: studies of their temperature dependence, binding characteristics, and specificity in vitro.

The lymphocytotoxicity of 33 lupus sera was tested against purified helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) subsets of T lymphocytes at 15 degrees C and 37 degrees C in vitro. There was significantly less killing of both OKT4 and OKT8 cells at 37 degrees C (p less than 0.001 and p less than 0.01) and the ratio of OKT4/OKT8 cell killing at 15 degrees C (1.39 (0.73); mean (SD] was different from that observed at 37 degrees C (0.79 (0.42)) (p less than 0.001). OKT4 killing was greater than OKT8 killing in 21 out of 33 sera at 15 degrees C, while 22 of these sera showed predominantly OKT8 cytotoxicity at 37 degrees C. The relation between the OKT4/OKT8 cell ratio and OKT4/OKT8 serum killing was examined in 22 patients at both temperatures: a significant inverse correlation was observed at 37 degrees C (r = -0.53; p = 0.015) but not at 15 degrees C (p greater than 0.05). The addition of metabolic and cytoskeletal inhibitors increased cytotoxicity at 37 degrees C, but not IgM surface binding. A Scatchard binding analysis of the reaction at 15 degrees C showed that large numbers of antibody molecules were bound to both subsets, with a low average dissociation constant of less than or equal to 6 x 10(-8) mol/l, and electrophoretic blotting indicated that the target surface antigens varied in type and number among individual lymphocytotoxic sera. The demonstration of temperature dependent, tight binding between lymphocytotoxic antibody and variable antigens on the T cell surface emphasises the potential for this phenomenon to affect lymphocyte function in vivo in patients with systemic lupus erythematosus.

Antibody Specificity↗