Specificity and degeneracy of T cells

The extent of T cell cross-reactivity is significant, even to the point where the terms "promiscuous" and "degenerate" apply. Degeneracy is an important feature of the immune response mechanism that permits effective T cell responses to a vast number of potential peptide sequences complexed to MHC molecules with specificity sufficient to distinguish between self and foreign peptides and thus to avoid autoimmune disease. Degeneracy at the clonal level of T cells also permits the use of very large combinatorial peptide libraries to identify and optimize peptide sequences that might be used for the treatment of T cell mediated autoimmune disease and for the design of vaccines for treatment of infectious diseases and cancer. Here we explore some recent findings derived from studies involving library scans of T cell lines and clones having clinically relevant specificities. In particular, we discuss two new insights: degeneracy among CD8 T cells appears to be substantially less than among CD4 T cells, and T cell clones characterized by a high affinity TCR interaction with a given pMHC complex are less degenerate than lower avidity T cells that require higher levels of pMHC complex for their activation.