PEPTIDES DETERMINE THE LIFE-SPAN OF MHC CLASS-II MOLECULES IN THE ANTIGEN-PRESENTING CELL

ALTHOUGH many peptides are generated during the intracellular processi ng of protein antigens, only a few are selected for recognition by the immune system(1-5). The immunodominant epitope of hen egg white lysoz yme (HEL) for H-2(k) mice is contained in a tryptic fragment of amino- acid residues 46-61 (refs 6, 7). The core of this T-cell epitope, from amino acids 52 to 61 (DYGILQINSR), contains those residues required f or binding to the class II molecule I-A(k) (ref. 7). Most of the natur ally processed fragments recovered from I-A(k)-bearing antigen-present ing cells (APCs) cultured with HEL contained this 52-61 core sequence, presented as a nested set of peptides with extensions at both the ami no and carboxyl termini(8). We now compare the handling by APCs of pep tides containing HEL 52-61 to establish whether there is an advantage for the APC in selecting extended peptides: different complexes betwee n peptides and major histocompatibility complex (MHC) molecules varied greatly in the amount of time associated with the APC, and in their i mmunogenic strength. This difference in persistence is one of the fact ors contributing to the selection and immune recognition of peptide-MH C complexes by T cells.