Hydrophobic amino acid residues in peptide antigens determine the genetic control of immune responses.

The ability to respond to an antigen is generally controlled by the activation of T helper cells. These cells are required for the initiation of immune responses including the activation of T effector cells in cell-mediated immunity and for the production of antibodies by B cells. Major histocompatibility complex (MHC) molecules present antigenic fragments to helper T cells, and recent studies suggest antigen binds to MHC molecules during this process. Both the composition and the structure of the peptide antigen and its ability to interact with MHC molecules determine the genetic responsiveness of an individual. We used a panel of synthetic polypeptide antigens with the repeating sequence Glu-X-Ala to determine the role that individual amino acid residues play in the recognition of antigens by T cells. The aromatic hydrophobic residues Tyr and Phe in polypeptide antigens Poly EYA, Poly EFA, and Poly EYAEFA were found to determine the genetic control of immune responses. Mice of H-2b,d haplotypes are high responders to Poly EYA, mice of H-2p,q haplotypes are high responders to Poly EFA and mice of H-2b,d,p,q strains are high responders to Poly EYAEFA. Mice of H-2k haplotype were nonresponders to all of these antigens. The antigen Poly ESA containing the hydrophilic residues (Ser), on the other hand, was found to be nonimmunogenic. Animals which are nonresponders to Poly EYA or Poly EFA, when primed with Poly EYAEFA, produce both T cells and antibodies which crossreact with Poly EYA and Poly EFA.(ABSTRACT TRUNCATED AT 250 WORDS)