T-cell colonies recognize antigen in association with specific epitopes on Ia molecules

Abstract

The products of the I region of the major histocompatibility complex have a role in many immunological processes and are intimately involved with, if not identical to, the genes controlling specific immune responses (Ir). Alloantibodies to I region-associated (Ia) antigens have proved extremely useful in defining the relationship between la antigens and Ir gene product function¹. We have recently reported data which suggest that monoclonal anti-Ia antibodies interact with different epitopes (antigenic determinants) on macrophage Ia molecules and that distinct epitopes, though on the same Ia molecule, are recognized by T cells in association with different antigens or antigen fragments². We have now used these monoclonal xenogeneic antibodies to guinea pig Ia antigens together with antigen-specific T-cell colonies to analyse further the role of macrophage Ia antigens in T-cell activation. We demonstrate here that the proliferative responses of individual antigen-specific T-cell colonies were often completely inhibited by only one of several anti-Ia monoclonal antibodies. These results strongly support the notion that monoclonal anti-Ia antibodies can be used to define epitopes on Ia molecules that have unique functions in the activation of antigen-specific T cells, and that individual T-cell colonies recognize antigen in association with functionally distinct epitopes on Ia molecules.