Biomedical subjects

A D Rees

Publications and source records attributed to A D Rees.

26 records · Page 2Linked to original sources

PubMed1987

Mapping of T cell epitopes using recombinant antigens and synthetic peptides.

Two complementary approaches were used to determine the epitope specificity of clonal and polyclonal human T lymphocytes reactive with the 65-kd antigen of Mycobacterium leprae. A recombinant DNA sublibrary constructed from portions of the 65-kd gene was used to map T cell determinants within amino acid sequences 101-146 and 409-526. Independently, potential T cell epitopes within the protein were predicted based on an empirical analysis of specific patterns in the amino acid sequence. Of six peptides that were predicted and subsequently synthesised, two (112-132 and 437-459) were shown to contain human T cell epitopes. This corroborated and refined the results obtained using the recombinant DNA sublibrary. Both of these regions are identical in M. leprae and M. tuberculosis and are distinct from the known B cell epitopes of the 65-kd protein. This combination of recombinant DNA technology and peptide chemistry may prove valuable in analysis of the cellular immune response to infectious agents.

Amino Acid Sequence↗

PubMed1987

T-cell activation by anti-idiotypic antibody: evidence for the internal image.

Human lymphoproliferative responses to a rabbit anti-idiotypic antibody (anti-Id TB71) and the corresponding mycobacterial protein antigen [38,000 molecular weight (MW)] have been investigated in a number of donors. It was found that responsiveness to anti-Id TB71 correlated with responder and non-responder (four subjects each) status to the 38,000 MW antigen. Furthermore, the induction of T-cell proliferation by both the 38,000 MW antigen and the anti-Id TB71 was dependent on accessory cells. When taken together with the concordance between the 38,000 MW antigen and anti-Id responsiveness, this implies that the 38,000 MW antigen and anti-Id TB71 stimulate related, or at least partially overlapping, repertoires of T cells. This was confirmed by the finding that cloned T cells reactive with the 38,000 MW antigen also proliferated in response to the anti-Id TB71. These observations are readily explained if the anti-idiotypic antibody contains an internal image of, and can therefore mimic, the antigen.

Animals↗

PubMed1985

Pulmonary sarcoidosis: alterations in bronchoalveolar lymphocytes and T cell subsets.

Peripheral blood and bronchoalveolar lavage lymphocyte subpopulations have been evaluated in 14 patients with pulmonary sarcoidosis and eight normal subjects, monoclonal antibodies of the leu series being used. No significant alterations of T lymphocyte subpopulations were found in the peripheral blood of sarcoidosis patients. There was, however, a significantly greater proportion of T suppressor-cytotoxic cells (36.0 (SD 17.6%] in the bronchoalveolar lavage fluid of patients than of normal subjects (15% (5.6%); p less than 0.01), but a decrease in the proportion of T helper-inducer cells (51.1% (18%) v 79.3% (9%). These changes correlated with the duration of the disease but not with other clinical, radiological, physiological, or biochemical criteria. Patients were followed up for six to 20 months and five patients had a repeat bronchoalveolar lavage and lymphocyte subpopulation evaluation after three to 14 months. The initial pulmonary T lymphocyte subset proportions were not predictive of clinical, physiological, or radiological alterations during follow up. There was also no consistent pattern in the relationship between change in T subset proportions and change in clinical physiological, and radiological features in the five patients having a repeat lavage. Lymphocyte surface marker studies may indicate immunopathogenetic mechanisms in sarcoidosis but do not appear to be good predictors of clinical outcome.

Adult↗

PubMed1985

Antigen specific human T cell clones: heterogeneity of specificity and function.

Human T cell clones specific for either mycobacterial or viral antigens have been generated and characterized. Different antigenic structures were recognized by T cells which had specific functions. These appeared to be directed at a number of target effector cells. Even where a number of T cell clones mediated the same function variation in clonal products suggested this might be achieved by different mechanisms. The multiplicity of immune function displayed by these T cell clones is discussed in the context of their antigenic specificity and genetic restriction.

Antigens, Bacterial↗

PubMed1985

Mycobacterial antigen-specific human T-cell clones secreting macrophage activating factors.

Macrophage activating factor (MAF) is produced by antigen-stimulated lymphocytes and activates macrophages for antimicrobial function. The capacity of individual microbial antigens to evoke and regulate this response has been explored using an affinity purified antigen (TB68) of Mycobacterium tuberculosis in combination with T-cell cloning. Four helper/inducer clones are described which responded strongly to this antigen. Three were specific, proliferating only to TB68 antigen and antigenic preparations containing this antigen. However, one of these clones (68.1) did not proliferate to BCG and PPD which contained the TB68 antigen. In addition, another clone, 68.13, also proliferated to other antigenic preparations which did not contain the TB68 antigen. Taken together, these data indicate the presence of several epitopes in the affinity-purified TB68 antigen. All the clones produced MAF, which enhanced H2O2 production in U937 cell lines and conventional macrophages matured from monocytes. Thus, T-cell clones proliferating to a mycobacterial antigen constitutively secrete lymphokines that activate macrophages to antimicrobial immunity.

Antigens, Bacterial↗

PubMed1984

Secretion of a macrophage-activating factor distinct from interferon-gamma by human T cell clones.

Supernatants from clones of human T lymphocytes that were responding to a purified Mycobacterium tuberculosis antigen were able to activate macrophages and macrophage-like myeloma cells (U937) to release increased amounts of the microbicidal agent hydrogen peroxide. The activity was not neutralized by monoclonal antibody against interferon-gamma (IFN-gamma), was greater than could be accounted for by the IFN-gamma activity in the supernatants, and was separated from IFN-gamma by high performance liquid chromatography. It is evident that IFN-gamma is not the only macrophage activator released by T lymphocytes responding to microbial antigen, and may not even be the main one to enhance antimicrobial activity in infections such as tuberculosis.

Antibodies, Monoclonal↗

PubMed1982

Is Peyronie's disease iatrogenic?

Three cases of Peyronie's disease are described, in which the condition is associated with hypertension and atherosclerosis. Another common factor is the use of beta-blocking agents in their treatment. A plea is made for an urgent review of the aetiology of Peyronie's disease bearing in mind the possibility of an iatrogenic cause.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Non-nominal HIV surveillance: preserving privacy while tracking an epidemic.

OBJECTIVE: To enhance HIV surveillance within a non-nominal provincial testing system. METHODS: Confirmatory HIV tests from a provincial laboratory were analyzed during 1995 and 1996. Enhancements included elimination of repeat positive tests for the same individual using automated matching of non-nominal identifiers and nurse call-back of health care providers, completion of missing information through call-back and connection of providers with resources for patient care. RESULTS: Forty-seven percent of 2,683 reactive HIV tests were identified as duplicates for the same individual, meaning that 1,401 people tested positive for the first time. From laboratory test data to enhanced unduplicated data after call-back, the proportion of tests for which risk and ethnic information was unknown dropped from 37% to 11% and from 64% to 18% respectively (p < 0.0001). CONCLUSIONS: Enhanced non-nominal surveillance for HIV is a practical means of marrying the needs of public health for epidemiological information and the rights of patients to privacy.

AIDS Serodiagnosis↗