Molecular Analysis of T Lymphocyte Recognition

Abstract

The mouse T cell clones that have been previously analyzed for allelic exclusion of T cell receptor genes were known to be either reactive to antigen-derived peptides bound to self major histocompatibility complex (MHC)-encoded molecules or alloreactive, that is able to recognize intraspecies allelic variants of self MHC molecules in the absence of exogenously added antigen. However, many T cell clones selected to respond to antigens in the context of self MHC molecules express a concomitant reactivity for allogeneic MHC molecules. Two main hypotheses have been proposed to explain the molecular basis of dual reactivity. The first states that dual reactive T cell clones possess a single αβ T cell receptor heterodimer that detects cross-reactive determinants shared by allogeneic MHC products and self MHC products complexed to foreign antigens. The second hypothesis considers that T cell clones with dual specificity violate allelic exclusion and express two different αβ T cell receptor heterodimers on their surface, one reacting with foreign antigen bound to syngeneic MHC products and the second with allogeneic MHC products. In order to distinguish between these two hypotheses and reveal whether the principle of allelic exclusion holds true for dual reactive T cells, we have analyzed all the T cell receptor α — and β — chain rearrangements present in a dual reactive T clone. Furthermore, in other experiments we have analyzed the contribution of the CD8 molecule to T-cell recognition.