Independent selection by I-A(k) molecules of two epitopes found in tandem in an extended polypeptide antigen

The protein hen egg white lysozyme (HEL) contains two segments, in tandem, from which two families of peptides are selected by the class II molecule I -A(k), during processing. These encompass peptides primarily from residues 31-47 and 48-63, Mutant HEL proteins were created with changes in residues 52 and 55, resulting in a lack of binding and selection of the 48-63 peptid es to I-Ak molecules. Such mutant HEL proteins donated the same amount of 3 1-47 peptide as did the unmodified protein. Other mutant HEL molecules cont aining proline residues at residue 46, 47, or 48 resulted in extensions of the selected 31-47 or 48-62 families to their overlapping regions (in the c arboxyl or amino termini, respectively). However, the amount of each family of peptide selected was not changed. We conclude that the presence or abse nce of the major peptide from HEL does not influence the selection of other epitopes, and that these two families are selected independently of each o ther.