Subtypes of HLA-B27 detected by cytotoxic T lymphocytes and their role in self-recognition

Breuning, Martijn H.; Lucas, C.J.; Breur, B. S.; Engelsma, M.; Lange, G. G. de; Dekker, A.; Biddison, William E.; Iványi, P

doi:10.1016/0198-8859(82)90018-0

Cited by 80 publications

(19 citation statements)

References 17 publications

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“…Studies with monoclonal antibodies and cytotoxic T lymphocytes indicated differences within the HLA-B27 molecule (36,37), but a recent clinical study did not identify a recognizable "pathogenic" HLA-B27 haplotype (25).…”

Section: Discussionmentioning

confidence: 96%

The risk of developing ankylosing spondylitis in HLA‐B27 positive individuals

Linden

Valkenburg

Jongh

et al. 1984

Arthritis & Rheumatism

437

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The present study was performed on 61 HLA-B27 positive first-degree relatives and 40 HLA-B27 negative relatives of 20 HLA-B27 positive probands with ankylosing spondylitis (AS). Of 24 HLA-B27 positive relatives 45 years or older, 21% had AS and 38% sacroiliitis. The HLA-B27 negative relatives did not have features of either disease. In the population study of 2,957 individuals 45 years or older, we found 5 cases of HLA-B27 positive sacroiliitis (according to the New York criteria) and 3 of these fulfilled the New York criteria for diagnosis of AS. In 2 of these 3 individuals, the diagnosis was made on clinical grounds. The phenotype frequency of HLA-B27 in this population is 7.8%, or about 230 HLA-B27 positive individuals in this population sample. Since AS was found in only 3 individuals, 1.3% of the HLA-B27 positive individuals in the population at large have AS; therefore, our data show that among individuals 45 years or older, 21% of HLA-B27 positive relatives of HLA-B27 positive AS patients have AS as compared with 1.3% of the HLA-B27 positive individuals in the population at large. Thus, the risk for AS is 16 times greater in the HLA-B27 positive relatives compared with HLA-B27 positive individuals in the population at large. The discriminatory value of the New York criterion of history of pain or the presence of pain at the dorsolumbar junction or in the lumbar spine was analyzed in the population and family studies and was found to be too nonspecific.

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Section: Discussionmentioning

confidence: 96%

The risk of developing ankylosing spondylitis in HLA‐B27 positive individuals

Linden

Valkenburg

Jongh

et al. 1984

Arthritis & Rheumatism

437

View full text Add to dashboard Cite

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“…4C and D) and CF (B7.3') ( Fig. 4A and B) which express subtypes of HLA-B27 [19] and B7 [16], respectively, that were not recognized by the CTL clones KOR-1 and KOR-132. As expected, neither of these inhibited lysis.…”

Section: Cold Target Inhibition As Avidity Assay For Ctl Clonesmentioning

confidence: 95%

Evidence for a regulatory role of the T8 (CD8) antigen in antigen‐specific and anti‐T3‐(CD3)‐induced lytic activity of allospecific cytotoxic T lymphocyte clones

et al. 1986

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The functional role of the T8 antigen of human T cells was studied by inhibition with anti-T8 monoclonal antibodies (mAb) of the cytotoxic action of T8+ cytotoxic T lymphocyte clones (CTL). All clones were allospecific and directed against HLA-B7. The ability of seven different anti-T8 mAb to inhibit the cytotoxicity of these alloreactive CTL clones corresponded with their avidity for a particular target cell. The lysis of cross-reactive antigen-bearing target cells was more readily blocked by anti-T8 mAb than lysis of the specific B7 target cell against which a clone was raised. The seven anti-T8 mAb showed a spectrum of CTL blocking ability ranging from strong blocking with all five CTL clones tested to weak inhibition of only two out of five clones. mAb inhibition of CTL reactivity and cold target inhibition studies with one of the five CTL clones indicate a post-binding role of the T8 molecule. Functional epitope mapping based on CTL blocking with the anti-T8 mAb resulted in the definition of one nonfunctional epitope on the T8 molecule which is only expressed on mature T lymphocytes and a cluster of closely related functional epitopes expressed on both thymocytes and mature T lymphocytes. Not only allospecific cytotoxicity, but also nonspecific cytotoxicity induced anti-T3 mAb in these allospecific clones was inhibited by anti-T8 mAb in the absence of HLA class I expression on the target cell (Daudi cell line). The hierarchy of blocking with anti-T8 mAb and the classification of functional epitopes on T8 in anti-T3-induced nonspecific cytotoxicity were similar to those obtained in blocking of allospecific reactivity of the CTL clones. This analogy points to an identical function of the T8 antigen in both allospecific and anti-T3-induced nonspecific cytotoxicity. If HLA class I molecules are the counter structures of the T8 antigen, then these results argue against an adhesion-like function of the T8 structure. The combined results show that the T8 molecule has a regulatory role in CTL activation. It is postulated that the T8 antigen might serve as a receptor that transduces a negative feedback signal for T cell activation which prevents T cell triggering by nonspecific interaction.

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“…"0 500,Ci of 125I lysate was incubated for 2 hours with 10 ,ul of monoclonal mouse serum and immune complexes were precipitated with staphylococcal protein A.11 Gel electrophoresis. Immune complexes were recovered in 8 M urea containing buffer and analysed as previously described.12 The isoelectric focusing (IEF) separating gel contained 2 0A) total ampholines, pH 3-10:pH [5][6][7] (1:4) (LKB, Wallac, Finland). The sodium dodecyl sulphate gel dimension was 12-5 % in acrylamide.…”

Section: Methodsmentioning

confidence: 99%