Influence of the T cell receptor alpha-chain on T cell reactivity and tolerance to Mls-1 in T cell receptor beta-chain transgenic mice

• Published in: The Journal of immunology (1950) Vol. 151; no. 2; pp. 556 - 565
• Main Authors: Blackman, MA, Smith, HP, Le, P, Woodland, DL
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15-07-1993; American Association of Immunologists
• Subjects: AIDS/HIV; Animals; Animals, Newborn - immunology; Biological and medical sciences; CD4-CD8 Ratio; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immune Tolerance; Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred CBA; Mice, Transgenic; Minor Lymphocyte Stimulatory Antigens - analysis; Minor Lymphocyte Stimulatory Antigens - immunology; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - physiology; T-Lymphocytes - immunology; Immune response; Cell function; T cell receptor; Rodentia; Beta-Peptide chain; Transgenic animal; Minor histocompatibility system; Vertebrata; Mammalia; Mouse; Immune tolerance; T-Lymphocyte; Alpha-Peptide chain; α/β T cell receptor
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.151.2.556

Previous analyses of a TCR V beta 8.1 transgenic mouse revealed multiple mechanisms of tolerance to the retroviral superantigen, Mls-1. Whereas some T cells were clonally deleted in the thymus, others became anergic in the periphery, or remained unaffected by the expression of Mls-1. In addition, a strong correlation between TCR alpha-chain usage and Mls-1 reactivity of individual transgenic V beta 8.1+ T cell hybridomas was established. Based on these observations, we speculated that the different mechanisms of tolerance were a consequence of the alpha-chain-mediated differences in Mls-1 reactivity. In the current studies, we make use of a V alpha 2-specific mAb to directly examine the role of the alpha-chain on tolerance in this transgenic model. We show, first, that V alpha 2+ CD4+ T cells, as a group, are relatively less Mls-1-reactive, and are elevated twofold in the periphery of Mls-1+ compared with Mls-1-V beta 8.1 transgenic mice. This elevated expression is also seen in the V alpha 2+ CD4+ population of mature thymocytes, but not in immature thymocytes. Second, Mls-1-induced neonatal tolerance in Mls-1-negative mice caused an increase of V alpha 2+ CD4+ T cells, comparable with the frequency of expression in transgenic mice that endogenously expressed Mls-1. Third, we have demonstrated a general correlation between the age-dependent increase in Mls-1-expression and the levels of V alpha 2+ CD4+ T cells during the first 4 wk of life. Taken together, these data suggest that the over-expression of V alpha 2+ CD4+ T cells in Mls-1+ mice is a consequence of mechanisms of tolerance, predominantly mediated by preferential lack of clonal deletion in the thymus. These data support the idea that clonal deletion is a competitive process and the influence of the TCR alpha-chain on the strength of Mls-1 reactivity of individual V beta 8.1+ transgenic T cells controls their susceptibility to clonal deletion.