Most T lymphocytes express a clonally distributed cell surface antigen receptor composed of disulfide-linked a and (3 subunits, noncovalently associated with several subunits called CD3 proteins . T cells that express the a/(3 form of the T cell receptor (TCR) recognize antigens in the context of cell surface proteins encoded by class I and class II genes of the major histocompatibility complex (MHC). A small distinct subset of peripheral T lymphocytes (

The specificity ofT lymphocytes derives from the properties ofclonally distributed membrane receptors . For most peripheral T cells (CD4+ CD8 -and CD4-CD8+), antigen is corecognized with molecules of the MHC by a receptor consisting ofclonally diverse aR heterodimers associated with the multichain CD3 complex (1-3). Recently, a subpopulation ofT cells was described, usually lacking expression of the CD4 and CD8 cell surface molecules, that uses as its receptor a distinct heterodimer (y8) associated with CD3 (4-7) . The specificity ofthis new TCR is not well characterized, although one report of reactivity with a polymorphic MHC-linked molecule has appeared (8).The genes encoding each ofthe chains of the two receptor heterodimers have been cloned and analyzed (9-15) . Each chain is encoded by a set of gene segments that undergoes rearrangement during differentiation of the T cell, although the number of such segments, their diversity in the germline, and the pattern of rearrangement varies for each locus. Ontogenetic studies have revealed that y and S are rearranged before R and a (14,(16)(17)(18)(19)(20), and T cells expressing y8-CD3 complexes on their cell surfaces appear in the murine thymus several days before a(3-CD3-expressing cells (21,22) .Investigation of TCR gene expression in various cloned cell lines has shown that most a(3-expressing cells lack an in-frame y gene rearrangement (23) and that most y8-expressing cells lack mRNA capable of encoding functional a or Q chains (4, 7) . In addition, the S locus is contained within the a locus, such that VaJa rearrangement will delete the S locus on that chromosome (14). These findings, together with biochemical studies showing mutually exclusive expression of one or the other of the types of TCR (aO or yS) on individual T cell clones and the ontogenetic pattern of receptor expression noted above (21), have led to the hypothesis that yS-and a(3-expressing T cells represent distinct lineages derived from a common precursor. Successful expression of a yS receptor is thought to preclude further receptor gene rearrangement, and hence, as expression. A failure to successfully rearrange either y or S permits continued rearrangement and the eventual expression of an a(3 receptor.

Targeted disruption of beta 2-microglobulin gene results in deficient major histocompatibility complex class I expression and failure to develop CD4-8+ T cells. Despite this, beta 2 M-/- mice reject skin grafts and cope with most viral infections tested. We asked whether CD4+8- cytotoxic T cells would play a role in compensating for the defect in CD4-8+ cytotoxic T cell function. We found that the cytotoxic activity against class II+ targets is significantly higher among CD4+8- T cells of beta 2M-/- than among those of beta 2M+/+ mice. In the limiting dilution experiment, we showed that the precursor frequency for the cytotoxic, CD4+8-, class II-specific T cells is at least fivefold higher in beta 2M-/- than in beta 2M+/+ mice. These results suggest that CD4+8- cytotoxic T cells could play a major role in carrying out cytotoxic function in beta 2M-/- mice.

The TCR-gamma and -delta chains of six murine hybridomas were compared by one-dimensional SDS-PAGE and two-dimensional NEPHGE/SDS-PAGE analysis. This allowed the identification of three distinct gamma chains (gamma a, gamma b, and gamma c) and three distinct delta chains (delta a, delta b, and delta c). Four gamma/delta chain combinations (gamma a delta a, gamma b delta b, gamma b delta c, and gamma c delta a) were observed. These results indicate that multiple forms of the delta chain are expressed and suggest that the delta chains are encoded for by an Ig-like rearranging gene. This delta chain polymorphism significantly enhances the potential diversity of TCR-gamma/delta, which may be of importance for a better understanding of the putative ligand(s) recognized by this receptor.

Antigen (HSA) bound in immune complexes at equivalence with syngeneic anti-HSA antibodies elicit much stronger humoral immune response then soluble HSA. On the other hand, administration of immune complexes formed with xenogeneic (rabbit) anti-HSA antibodies suppressed humoral immune response against HSA, but not against rabbit IgG in mice. We suggest that immunization with antigen bound in immune complex might represent a powerful tool in enhancing humoral immune responses.