This is a revision of a previously submitted proposal to study peptide-HLA Class II interactions. Both promiscuous and allele-specific peptide-Class II interactions will be studied, particularly with respect to competition by alleles for promiscuous peptides and the influence of neighboring peptides upon the function of another peptide. The influence of the microenvironment within the cell upon the formation of peptide-Class II complexes will also be studied. For allele-specific peptides, the investigators will test whether linked allele-specific epitopes can lead to cryptic determinants during antigen processing. The investigators have now adapted their system to a more "natural" one of binding of exogenously administered peptides to living cells, rather than to purified Class II molecules as in their previous application. Their measurements of binding are 1) through proliferation of a T cell clone specific for the antigen and 2) direct visualization after isolation of Class II molecules bound to the peptide.