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Genetic analyses indicate that genes within the major histocompatibility complex (MHC) can be involved in susceptibility to autoimmune disease. To investigate the role of the tumour necrosis factor beta (TNFB) gene in myasthenia gravis (MG) susceptibility, we analysed an NcoI polymorphism within the TNFB gene in 63 MG patients and 93 healthy individuals. When patients were subdivided according to thymic pathology, we found differences between MG patients with thymic hyperplasia and thymoma versus controls. In MG patients with thymic hyperplasia we found a positive association with the TNFB*1 allele [Relative risk (RR): 2.6; P < 0.001] and phenotype (RR: 1.8; P < 0.005) and a negative association with the TNFB*2/2 genotype (RR: 0.2; P < 0.001) when compared to the controls. On the other hand, in MG patients with thymoma we found a positive association with the TNFB*2/2 genotype (RR: 5.6; P < 0.01) and a negative association with the TNFB*1 allele (RR: 0.3; P < 0.05) and *1/2 genotype (RR: 0.2; P < 0.01). These data suggest that the two different forms of MG can have different pathogenesis and that the TNFB gene could influence susceptibility to MG.

SUMMARY Twenty-two subjects (11 HLA A1 B8 DR3, 11 non-A1 B8 DR3) were tested for the capacity of their lymphocytes to express Tac molecules and interleukin-2 (IL-2) receptors (quantified using radiolabelled IL-2) after mitogen stimulation. Ten of these subjects (five Al B8 DR3 and five non-A1 B8 DR3) were also tested for the ability of their lymphocytes to proliferate under IL-2 stimulation. Al B8 DR3 subjects express a normal number of high-affinity IL-2 receptor sites, but the affinity of these receptors sites is significantly increased. Unexpectedly, Al B8 DR3 lymphoblasts show a lower response to IL-2 than non-Al B8 DR3 for high doses of recombinant IL-2.

SUMMARY Two human alloantisera, previously described as possibly detecting new beta 2-microglobulin associated proteins, selectively expressed on HLA-A2 and HLA-A1 phytohaemagglutinin (PHA)-activated lymphocytes, immunoprecipitated only molecules with the same isoelectric point as HLA-A1 and A2 products. This result suggests that the selected alloantisera do not react with the products of an HLA class I locus different from ABC but probably recognize a new epitope arising on HLA-A molecules upon conformational changes consequent to cell activation.