Immune recognition and effector function in subsets of CD4 T cells.

T cells expressing the cell surface differentiation antigen CD4 are involved in most immune responses. Our studies address two issues about CD4 T cell responses to antigen: first, how does the T cell receptor come together with its ligand to generate an immune response, and what is the role of the CD4 molecule in this response? Second, are all CD4 T cells identical in their functional activity, and how does the activating signal determine the functional outcome of a response? Our studies outlined below suggest that the T cell receptor and its peptide: class II major histocompatibility complex (MHC) molecule ligand come together in a defined orientation determined in part by the binding of CD4 to both the T cell receptor and its ligand. Our studies suggest that the V beta chain is involved directly in MHC antigen recognition, binding self MHC with low affinity and non-self MHC with high affinity. The selective effect of the Mls locus on V beta expression is believed to reflect the binding of the Mls protein directly to the V beta region. CD4 is described as a co-receptor, forming an inducible part of the T cell receptor and binding to the same class II MHC molecule as that receptor. Studies with both cloned lines and normal CD4 T cell populations suggest the existence of two separable subsets with definable function. One set appears to be specialized for the activation of the humoral immune response, while the other drives the cell-mediated immune responses, particularly those involving the activation of macrophages. These two subsets of CD4 T cells have differential activation requirements, seen particularly in the requirement for interleukin 1 (IL-1) in the activation and clonal expansion of CD4 T cells involved in humoral immunity. This requirement for IL-1 may also be observed in the priming of this subset of CD4 T cells. These studies demonstrate that the optimal activation of CD4+ T cells involves recognition of peptide fragments presented by class II MHC molecules and accessory signals derived from the antigen presenting cells.