PubMed Health⌕ Search

Biomedical subjects

M López-Botet

Publications and source records attributed to M López-Botet.

At least 73 records · Page 4Linked to original sources
PubMed1991

A novel functional cell surface dimer (Kp43) expressed by natural killer cells and gamma/delta TCR+ T lymphocytes. II. Modulation of natural killer cytotoxicity by anti-Kp43 monoclonal antibody.

In the present study we provide the first evidence supporting the fact that the Kp43 NK-associated cell-surface dimer may be involved in regulating MHC-unrestricted cytotoxicity. Our results indicated that incubation of IL-2-activated NK cells in a 51Cr-release assay with either the Kp43-specific mAb or its F(ab')2 fragments induced a significant cytolytic activity directed against normal autologous and allogeneic T cell blasts, which are relatively resistant to NK cell-mediated lysis. The cytotoxic effect was not observed in fresh CD3- CD16+ CD56+ Kp43+ lymphocytes and was only substantiated in IL-2-preactivated NK cells. Although stimulation with the Kp43-specific mAb did not significantly change the intracellular Ca2+ concentration, both Ca2+ and Mg2+ were required for the induction of cytotoxicity. The anti-Kp43-mediated activation of cytolysis was inhibited by anti-CD18 and CD11a mAb, whereas it was not significantly altered by either CD11b, CD11c, CD2, or LFA-3-specific mAb, rendering unlikely the participation of the latter. In contrast to these results the Kp43-specific mAb did not enhance the high levels of spontaneous cytotoxicity mediated by IL-2-activated NK cells against a panel of different tumor cell lines. An inhibitory effect mediated by anti-Kp43 mAb on the IL-2-dependent proliferation of NK cells was previously reported and appears, at least partially, secondary to the induction of an autolytic mechanism that is synergistically enhanced by anti-CD16 mAb. Altogether our results point out that interaction of the Kp43 dimer with its specific mAb is capable of inducing cytolytic activity and suggest that the molecule may play an important functional role in lymphokine-activated NK cells.

Antibodies, Monoclonal↗
PubMed1991

Identification of natural killer (NK) cells in lesions of human cutaneous graft-versus-host disease: expression of a novel NK-associated surface antigen (Kp43) in mononuclear infiltrates.

We performed an immunohistochemical analysis of skin biopsies from 13 allogeneic bone marrow transplant (BMT) recipients, undergoing either acute graft-versus-host-disease (aGVHD, n = 8) or chronic GVHD (cGVHD, n = 5). A panel of different monoclonal antibodies (MoAb) was employed including anti-CD2, -CD3, -CD4, -CD8, -CD11b, -CD16, -CD56, and -CD57, as well as a recently described reagent (HP-3B1) specific for a novel natural killer (NK)-associated cell-surface antigen (Kp43). Our data indicate that in aGVHD lesions the proportions of CD2+ cells often exceeded those detected with anti-CD3 MoAb. Double labeling confirmed the presence of CD2+ CD3- lymphocytes and suggested the coexpression in some cells of CD2 and CD11b. When MoAb specific for non-lineage-restricted NK-associated markers were employed, anti-CD56 and -CD57 occasionally stained variable numbers of lymphocytes (means = 14.6% of mononuclear cells in 0.05 mm2, range less than 1-48% and means = 10.3%, range 2-25%, respectively), whereas no CD16+ lymphocytes were observed. In contrast, most samples consistently displayed substantial proportions of Kp43+ cells (means = 32.8%, range 12-63%), which appeared CD3- and were mainly located at the dermoepidermal junction. On the other hand, sections from most (four of five) cGVHD lichenoid lesions analyzed displayed lower proportions of Kp43+ and CD56+ cells. Our data point out the interest of the anti-Kp43 MoAb to identify NK cells in aGVHD lesions, suggesting their pathogenetic participation.

Adolescent↗
PubMed1990

A novel functional cell surface dimer (Kp43) expressed by natural killer cells and T cell receptor-gamma/delta+ T lymphocytes. I. Inhibition of the IL-2-dependent proliferation by anti-Kp43 monoclonal antibody.

In the present study we describe a novel functional cell surface molecule, designated as Kp43, which is expressed among leukocytes by NK cells, TCR-gamma/delta + T lymphocytes, and some CD8+ CD56+TCR-alpha/beta + T cell clones. The Kp43 Ag is a 70-kDa disulfide-linked dimer, which migrates in SDS-PAGE under reducing conditions as a single 43-kDa band. Two-color immunofluorescence staining of fresh PBL revealed that only a fraction of CD16+, and of TCR-gamma/delta + T lymphocytes expressed the Ag. The analysis of TCR-alpha/beta + T cell clones showed that a small proportion (2 out of 20) weakly expressed Kp43 together with the CD8 and CD56 molecules. By immunoperoxidase staining of different tissues the anti-Kp43, reactivity was detected exclusively in lymphoid organs, where a minority of scattered cells was stained, and in some liver sinusoidal cells. Essentially all NK cells acquired Kp43 when stimulated with a B lymphoblastoid cell line. By contrast, the pattern of distribution of Kp43 remained stable upon in vitro culture of T-gamma/delta lymphocytes, thus delineating two subsets according to its expression. In lymphokine-activated killer populations, obtained by culturing either PBL or NK cells with high concentration of IL-2, most CD16+ and CD56+ cells became Kp43+. The Kp43-specific mAb inhibited the IL-2-dependent proliferative response of cultured NK and TCR-gamma/delta + T cells without affecting their non-MHC-restricted cytotoxicity. The partial inhibitory effect, which was mediated as well by pepsin digested F(ab')2 fragments, was lost upon reduction to Fab. The anti-Kp43 mAb did not interfere with the specific binding of IL-2 to its surface receptors. Altogether the data point out that the Kp43 dimer is involved in the regulation of the IL-2-dependent proliferative response of NK cells and a subset of TCR-gamma/delta + T lymphocytes.

Antibodies, Monoclonal↗
PubMed1990

Expression of a novel activation antigen on intrahepatic CD8+ T lymphocytes in viral chronic active hepatitis.

It has been suggested that CD8+ T lymphocytes play an important role in the pathogenesis of liver cell injury in viral chronic active hepatitis. However, the mere presence of T lymphocytes with cytotoxic/suppressor phenotype in the hepatic inflammatory infiltrate does not necessarily imply that these cells are actively involved in an immune reaction. In the present study, the expression of different activation antigens have been investigated, such as the interleukin-2 and the transferrin receptors and a recently described T-cell activation molecule termed "activation-inducer molecule" on the different lymphocyte subsets of both peripheral blood and liver-infiltrating lymphocytes from patients with virus-induced chronic active hepatitis. Studies of double immunostaining clearly showed that the majority of intrahepatic CD8+ T lymphocytes selectively coexpressed the activation-inducer molecule, whereas no significant expression of this molecule was found on either intrahepatic CD4+ T lymphocytes or peripheral blood lymphocytes of the same patients. Furthermore, lymphocytes from both peripheral blood or liver compartments did not express other activation antigens such as the interleukin-2 and the transferrin-receptor molecules. These results suggest that the CD8+ T-cell subset bearing the activation-inducer molecule may represent the main activated intrahepatic lymphoid cell population in virus-related chronic active hepatitis.

Adult↗
PubMed1990

Relation between the increase of circulating CD3+ CD57+ lymphocytes and T cell dysfunction in recipients of bone marrow transplantation.

Some patients undergoing bone marrow transplantation (BMT) persistently present increased proportions of circulating CD57+ T cells. We analysed the cell surface phenotype in peripheral blood mononuclear cells (PBMC) from 69 allogeneic and 11 autologous BMT recipients. In parallel samples from 49 patients, the proliferative response to T cell mitogens was assessed, either in the presence or absence of exogenous interleukin-2 (IL-2). PBMC samples from long-term allogeneic BMT patients with increased proportions of CD57+ cells displayed significantly (P less than 0.001) lower proliferative responses, compared with samples from patients with normal proportions of CD57+ cells and from healthy subjects. Elimination of the CD57+ population by C'-dependent lysis did not normalize the proliferative response. After positive selection by cell sorting, CD57+ cells responded poorly, but in the presence of IL-2 the proliferation appeared to be similar to that displayed by the CD57- subset and still suboptimal compared with normal controls. These data suggest that the hyporesponsiveness to mitogenic stimuli in the presence of exogenous IL-2 of PBMC from allogeneic BMT recipients cannot be simply attributed either to the putative suppressor activity of CD57+ cells, or to a poor proliferative capacity of this subset. Supporting this notion we report that PBMC from long-term autologous BMT recipients containing high proportions of CD57+ T cells respond normally to T cell mitogens.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Deficient protein kinase C-dependent Na+/H+ exchanger activity in T cells from bone marrow transplantation recipients.

The early Na+/H+ exchanger-mediated alkalinization of intracellular pH (pHi) was analyzed in peripheral blood T cells from 23 bone marrow transplantation (BMT) recipients (17 allogeneic and 6 autologous) and a group of 13 healthy controls, in response to stimulation of protein kinase C (PKC) with a phorbol ester. In parallel we evaluated the proliferative response of peripheral blood T cells to an anti-CD3 mAb in the presence of either IL-2 or PMA. The pHi increase (delta pHi) observed in control samples ranged from 0.14 to 0.23 pH units (X +/- SD = 0.17 +/- 0.03). In 10 allogeneic and four autologous BMT recipients the delta pHi was under the lower limit of the control range (range: 0.01 to 0.09, X +/- SD = 0.05 +/- 0.02), whereas the remaining nine cases responded similarly to control samples (range: 0.14 to 0.24, X +/- SD = 0.17 +/- 0.04). The response of the Na+/H+ antiporter to a PKC-independent osmotic stimulation appeared to be normal, thus indicating that the intrinsic Na+/H+ exchanger activity was unaltered. The anti-CD3 induced proliferative response of the group of samples displaying a suboptimal delta pHi, was significantly lower (p less than 0.01) than that detected in control samples. T cell proliferation in samples from BMT recipients displaying a normal delta pHi was undistinguishable from the control group (p greater than 0.05). Our results provide the first evidence for a defective early metabolic event, closely related to PKC activity, in T cells from BMT recipients displaying a low proliferative response to T cell mitogens.

Bone Marrow Transplantation↗
PubMed1989

High toxic efficiency of ricin immunotoxins specific for the T-cell antigen receptor of a human leukemia T-cell line.

Immunotoxins (ITs) were prepared by covalently coupling ricin to monoclonal antibodies (MAbs) directed against: (a) 2 different epitopes of the T-cell receptor (TcR) expressed by the Jurkat leukemia T-cell line (JTi2 and JTi4 MAb), (b) 2 epitopes of the CD3 complex (SpV-T3b and 11D8 MAb), (c) the CD2 and the CD8 cell-surface molecules. Conjugates were assayed for their cytotoxic activity by pre-incubating the Jurkat cell line with different concentrations (10-250 ng/ml) of each IT for 2 hr at 37 degrees C in the presence of 0.1 M lactose. After washing, cells were cultured for 24 hr and their protein synthesis and proliferative capacities were assessed. Dose-response experiments indicated that JTi2, JTi4 and anti-CD3 (11D8) ITs inhibited by greater than 90% the cell line proliferation at 50 ng/ml, a 5-fold lower concentration than that required to achieve a similar effect when anti-CD2 and anti-CD3 (SpVT3b) were used. After 4 hr of culture subsequent to treatment with JTi2 or JTi4 ITs (250 ng/ml), protein synthesis was inhibited (greater than 80%). By limiting dilution analysis (LDA) we estimated that the frequency of proliferating Jurkat cells (1/1.5) was reduced to 1/20, 1/460 and 1/300 after treatment with anti-CD3 (SpVT3b), JTi4 and JTi2 ITs, respectively. Phenotypic analysis of 13 clones derived from JTi2 IT-treated Jurkat cells showed that 50% were CD7+ CD3- JTi- variants. When bone-marrow mononuclear cells, previously mixed with low concentrations of Jurkat cells, were treated with anti-JTi ITs, the toxic efficiency estimated by LDA was maintained whereas the growth of CFU-GM remained unaltered.

Antibodies, Monoclonal↗
PubMed1989

Induction of T cell function via the gp33/27 activation inducer molecule (AIM) requires co-expression of the CD3/TcR complex.

Monoclonal antibodies specific for a dimeric cell surface activation antigen (gp33/27), preliminary designated as activation inducer molecule (AIM), are capable of triggering interleukin 2 (IL 2) synthesis, IL 2 receptor expression and T cell proliferation when used in conjunction with phorbol esters. We have analyzed the functional relationship between the AIM and the CD3/TcR-mediated activation pathways. Transient modulation of the CD3/TcR complex in the Jurkat cell line, as well as the stable loss of the CD3/TcR surface expression in variant subclones, determined an inhibition of the IL 2 production triggered by anti-AIM monoclonal antibody (mAb). In contrast, neither the surface expression of AIM nor the ability to respond to a Ca2+ ionophore were affected. Similar results were observed in peripheral blood T lymphocytes, detecting after CD3 modulation an inhibition of both the IL 2 synthesis and the proliferative response to anti-AIM mAb. Altogether our data indicate that the activation pathway triggered by anti-AIM mAb is functionally linked to the expression of the CD3/TcR complex in mature T cells.

Antigens, CD↗
PubMed1989

Expression of a gp33/27,000 MW activation inducer molecule (AIM) on human lymphoid tissues. Induction of cell proliferation on thymocytes and B lymphocytes by anti-AIM antibodies.

We have recently described several monoclonal antibodies (mAb) that recognize a heterodimeric structure (gp33/27,000 MW) expressed on the surface of human peripheral blood T lymphocytes upon activation with different mitogenic stimuli. Such mAb, when used in combination with submitogenic doses of phorbol ester, were capable of triggering T-cell proliferation. The antigen has been designated as activation inducer molecule (AIM). In the present study we have investigated the expression of the AIM in different lymphoid and non-lymphoid tissues. In addition, we have analysed the ability of lymphocyte subsets derived from thymus and tonsil to proliferate in response to anti-AIM mAb. The presence of AIM on subpopulations of lymphoid cells from thymus, tonsil, lymph node and spleen has been demonstrated by immunoprecipitation, flow cytometry and immunoperoxidase staining of tissue sections. By contrast, non-lymphoid cells from tissue such as brain, kidney, liver, lung or skin did not react with anti-AIM mAb. In thymus, the AIM expression was restricted to a subset of CD3+ medullary thymocytes, whereas CD1+ CD3- cortical thymocytes did not express this antigen. Nevertheless, the majority of both purified CD1- and CD3- thymocytes expressed AIM antigen after treatment with PMA. In tonsil and lymph node, a strong staining of a subset of CD3+ T lymphocytes located in the germinal centre was observed by immunohistochemical labelling with anti-AIM mAb. Certain T cells from the paracortical zone and CD19+ B lymphocytes from mantle region were also reactive. Both purified tonsillar T and B lymphocytes strongly expressed AIM after activation with PMA. The anti-AIM mAb was able to induce a strong proliferative response on purified CD1- thymocytes as well as on both purified tonsillar T and B lymphocytes in the presence of submitogenic doses of PMA. By contrast, no proliferative response was induced through the AIM in the CD3- immature thymocyte subset.

Antibodies, Monoclonal↗
PubMed1988

Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes.

In this report, we describe a novel activation antigen that appears very early after T cell activation and is absent in resting lymphocytes, through which agonistic proliferative signals can be triggered by mAb binding. It has been designated as activation inducer molecule (AIM) and is a disulphide-linked heterodimeric structure containing two polypeptide chains of Mr 33,000 and 27,000. The expression of AIM can be induced by different activation stimuli such as PMA, PHA, or anti-CD3 mAb, but not by the Ca2+ ionophore A23187, and it precedes the expression of other activation molecules such as 4F2 or the IL-2-R. Once AIM antigens are expressed on lymphocytes after stimulation with submitogenic doses of PMA, the binding of anti-AIM mAbs triggers a strong proliferative response. Furthermore, a comitogenic effect of the anti-AIM mAbs is exerted in the presence of either PHA or anti-CD3 mAb. The activation of lymphocytes through AIM antigens induces both IL-2 and IL-2-R receptor synthesis and is inhibited by anti-IL-2-R mAbs.

Antibodies, Monoclonal↗
PubMed1988

Triggering of co-mitogenic signals in T cell proliferation by anti-LFA-1 (CD18, CD11a), LFA-3, and CD7 monoclonal antibodies.

Proliferative T cell responses were elicited in a comitogenic assay when purified mAb against CD 18, CD11a, LFA-3, and CD7 were immobilized onto solid plastic surfaces together with submitogenic doses of mAb against the CD3 complex. The proliferative response was associated to the production of IL-2 and to the expression of IL-2R. We explored the possibility that a second signal provided by either PMA or a Ca2+ ionofore could replace the anti-CD3 mAb in the comitogenic assay. Interestingly, our data clearly indicate that PMA but not the ionofore was capable of mediating the co-mitogenic effect in conjunction with solid-bound mAb (CDw18, CD11a, LFA-3, and CD7). We also demonstrate that the mAb (anti-CD4 and anti-CD2) which have been previously described as co-mitogenic in combination with anti-CD3 are capable of eliciting this activating signal in the presence of PMA. These data indicate that mAb to certain cell surface differentiation Ag that in soluble form inhibit T cell function such as LFA-1, LFA-3, and CD2 can under appropriate conditions induce co-mitogenic signals on T cells. Our results support the hypothesis that several cell surface differentiation Ag may participate in conjunction with the T3-Ti complex in the transmembrane signal transduction leading to T cell activation.

Antibodies, Monoclonal↗
PubMed1988

CD2 is involved in regulating cyclic AMP levels in T cells.

The human T lymphocyte-specific CD2 (T11) molecule, that regulates T cell activation, is capable of mediating increases of intracellular cAMP. Monoclonal antibodies directed to different epitopes of the CD2 molecule which either induce or inhibit T cell proliferation are capable of triggering an increase of cAMP comparable to that induced by reagents which activate adenylate cyclase. These results indicate that there is a relationship between the CD2 membrane molecule and the adenylate cyclase system.

Adenylyl Cyclases↗
PubMed1988

Prostaglandin E2 and the increase of intracellular cAMP inhibit the expression of interleukin 2 receptors in human T cells.

We have analyzed the effect mediated by prostaglandin E2 (PGE2) and different reagents that increase intracellular cAMP on the expression of the p55 subunit (CD25) of interleukin 2 receptors (IL 2R), on the levels of CD25-specific mRNA and on the expression of high affinity IL 2R. In purified T cells, activated either by an anti-CD3 monoclonal antibody or phytohemagglutinin, the addition of PGE2 (10(-6) M), forskolin (5 X 10(-5) M), cholera toxin (0.2 microgram/ml) or dibutyryl cAMP (dBcAMP) (10(-4) M) decreased the cell surface expression of IL 2R by reducing (40%-78% inhibition) the proportions of CD25+ cells as well as the expression of high affinity IL 2R, detectable after 24 h. Furthermore, it was observed that PGE2 reduced the concentration of IL 2R-specific mRNA after a 6-h period of activation, indicating that its regulatory activity takes place at a pretranslational level. The addition of exogenous recombinant IL 2 only partially reversed the inhibition, thus suggesting that PGE2 and increased intracellular concentration of cAMP directly interfered with CD25 expression and that their effect could not be merely attributed to a lack of IL 2-dependent positive feedback. Cells cultured under the same conditions in the presence of phorbol myristate acetate, that activates protein kinase C, were refractory to the cAMP-mediated regulation. Finally, we demonstrate that both PGE2 and dBcAMP inhibit the generation of inositol metabolites after T cell activation, thus indicating that these reagents interfere with early signal transduction mechanisms which precede the synthesis of IL 2R.

Antigen-Antibody Reactions↗
PubMed1988

Selective T cell subset depletion with anti-CD4 and anti-CD8 intact ricin immunotoxins.

In the present study we have comparatively analysed the specific activity of a panel of immunotoxins (ITs) prepared by coupling Ricin to several monoclonal antibodies (MoAbs) directed against the CD3, CD4 and CD8 T cell membrane molecules. Peripheral blood and bone marrow mononuclear cells (PBMC and BMMC) were incubated with the different ITs for 2 h, in the presence of 0.1 M lactose, washed and subsequently stimulated with either phytohemagglutinin (PHA) or an anti-CD3 MoAb. Our results indicate that the proliferative response of PBMC to both stimuli was specifically inhibited (greater than 95%) by either anti-CD3 IT or a combination of anti-CD4 and CD8 ITs, at concentrations comparable to those previously used for ex vivo T cell depletion (300 ng/ml). When used individually at the same dose, anti-CD8 and anti-CD4 ITs inhibited the PHA-induced PBMC proliferative response 40 and 70% respectively. When either anti-CD4 or anti-CD8 IT-treated cells were activated with PHA and cultured for 14 days in the presence of IL-2, less than 2% of the blasts expressed the corresponding antigens as assessed by flow cytometry analysis. Similar results were observed when BMMC were treated with the different ITs. In contrast, the growth of CFU-GM was minimally affected (0-25% inhibition). Our data indicate that ITs directed against T cell subsets are highly active and specific reagents that may be potentially useful for pre-transplant bone marrow purging.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Defective interleukin 2 receptor expression is associated with the T cell disfunction subsequent to bone marrow transplantation.

In the present work we have used monoclonal antibodies (mAb) as probes to attempt a dissection of the mechanisms underlying the immunodeficiency subsequent to bone marrow transplantation (BMT). To this end we have studied 19 allogeneic BMT recipients, analyzing the proliferative response of peripheral blood mononuclear cells (PBMC) after activation with either phytohemagglutinin (PHA), anti-CD3 or anti-CD2 mAb. All patients presented normal proportions of CD2+ and CD3+ lymphocytes, as assessed by flow cytometry. Our results indicated that in most cases both CD2 and CD3-mediated activation pathways were inefficient to trigger normal T cell proliferation. The addition of exogenous interleukin 2 (IL2) did not restore in most cases the proliferative response, pointing out that additional defects contribute to the hyporesponsiveness. This was more evident in the group of patients studied during the first 6 months. To further dissect the T cell defect we analyzed the effect of a phorbol ester (phorbol myristate acetate, PMA), which activates protein kinase C, on the anti-CD3-induced response. Our data showed that PMA synergized with anti-CD3 similarly to exogenous IL2, and restored the proliferative response only in certain cases. The expression of IL2 receptors (CD25) as assessed by cytofluorimetry, after either PHA or anti-CD3 and PMA stimulation, was shown to be depressed, and the addition of IL2 did not restore it. Finally, we observed that the early increase of intracytoplasmic Ca2+ after anti-CD3 stimulation was comparable to that detected in normal PBMC. Altogether these results indicate that a diminished CD25 expression is associated with the T cell defect, and cannot apparently be attributed to an inability of the CD3 molecule to transduce early activation signals thus suggesting that either protein kinase C itself or an as yet undefined metabolic step preceding IL2 receptor expression is abnormal in variable proportions of T cells after BMT, and constitutes another manifestation of this complex immunodeficiency.

Antibodies, Monoclonal↗
PubMed1987

An in vivo functional immune system lacking polyclonal T-cell surface expression of the CD3/Ti(WT31) complex.

A polyclonal T-cell receptor complex (TCR) expression defect (as detected with monoclonal antibody WT31) has been found in two children belonging to an otherwise healthy Spanish family. One of the sibs (V, who had been vaccinated with attenuated poliomyelitis virus) showed clinical signs of immunodeficiency with an autoimmune syndrome, but the other (older) sib (D, vaccinated with attenuated rubella, measles, mumps, and poliomyelitis viruses) has been symptomless throughout life. In contrast to both sibs' normal expression of other peripheral leucocyte markers, as measured by flow cytometry (including CD1, CD2, CD4, CD8, and CD16), only about 6% of CD2+ polyclonal T cells expressed surface antigen-specific T-cell receptor (Ti/WT31), and only about 23% weakly expressed surface CD3 determinants. On the remaining CD2+ T cells in each sib the expression of Ti and CD3 was undetectable; the defect in CD3 expression is very likely secondary to the defect in Ti expression. Natural killer (NK) activity was not increased in any of the sibs, ruling out a high content of NK cells among their CD2+ lymphocytes. Functional data indicate that CD3-mediated T-cell activation with anti-CD3 monoclonals and Ti-mediated responses to allogeneic and tetanus toxoid antigens were severely depressed, whereas activation via CD2 was normal in the T lymphocytes of both sibs. Genes encoding for Ti alpha, beta, and gamma chains did not show major alterations by southern blot analysis, and polyclonal beta chain genes rearrangements were detected in both children's T-cell blasts. Family clustering suggests a genetic pathogenesis, but linkage to HLA or other blood group markers has not been found. Sib V had a concomitant autoimmune disease and died after a severe autoimmune haemolytic anaemia, indicating a relationship between the TCR and generation of autoimmune clones. However, the resistance of both individuals to infection and to vaccination with attenuated viruses, and the fact that sib D has been symptomless to date questions the relative importance of the TCR in the immune response against infection, and suggests that alternative T-cell activation pathways and non-specific defence mechanisms (external surfaces--bound and/or cellular) may suffice under certain circumstances.

Adult↗