Individual T cell receptor (TCR) Valpha elements are expressed preferentially in CD4 or CD8 peripheral T cell subsets. The closely related Valpha3.1 and Valpha3.2 elements show reciprocal selection into CD4 and CD8 subsets, respectively. Transgenic mice expressing site-directed mutants of a Valpha3.1 gene were used to show that individual residues in either the complementarity-determining region 1 (CDR1) or CDR2 were sufficient to change selection from the CD4 subset to the CD8 subset. Thus, the germline-encoded Valpha elements are a major influence on major histocompatibility class complex (MHC) restriction, most likely by a preferential interaction with one or the other class of MHC molecule.

SummaryEvaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg 13 or Arg7~ 71. Among TL patients, 87% carry specific alleles of DRB1 Arg 13 or ArgT~ 71 as compared to 43% among controls (p = 5 • 10 -6) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the [3 chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule.

Antibodies to Ro (SSA) and La (SSB) cellular ribonucleoprotein complexes are found in the circulation of patients with Sjögren's syndrome (SS), mainly in those with the primary form of the syndrome. Their presence is associated with long disease duration, earlier disease onset, parotid gland enlargement, systemic manifestations and also with hypergammaglobulinemia, rheumatoid factors and monoclonal type II cryoglobulins. While anti-Ro (SSA) antibodies are not specific for SS, anti-La (SSB) antibodies seem to be specific. Studies of HLA class II molecules in Ss patients with and without these antibodies have shown that their production is under genetic control. Finally, there is no conclusive evidence relating pathogenetically these autoantibodies to tissue destruction in SS.

The inhabitants of Metsovo in northwestern Greece have been environmentally exposed to asbestos from childhood because they had been using a tremolite-containing material for whitewash, without knowing its consistency. As a result, they have a very high incidence of calcified pleural plaques and malignant pleural mesothelioma but no pulmonary fibrosis. In the present study we examined certain aspects of the humoral immunity in the serum of 109 individuals: levels of immunoglobulins, C-reactive protein and complement components, as well as the presence of antinuclear antibodies, rheumatoid factor, antibodies to extractable nuclear antigens, to ds-DNA and to cardiolipin. Our results show that, compared to controls, those exposed to asbestos have increased IgG and C₃ levels. Those with pleural plaques have, in addition, increased IgA levels and an increased incidence of antinuclear antibodies. The results of the study suggest that nonoccupational asbestos exposure affects humoral immunity. The presence of pleural plaques accentuates this effect.

Mice homozygous for the gld or lpr mutations develop autoimmunity, and a lymphoproliferative disorder involving accumulation of huge numbers of unusual CD4-CD8-TCR alpha beta lo T cells. Here we review our past work with gld mice, and attempt to explain lymphoproliferation in terms of current models of T cell maturation and self-tolerance induction. The availability of molecular probes to the gene products of lpr and gld should shortly lead to a better understanding of the acquisition of self tolerance during T cell maturation and of autoimmunity.