We isolated and identified naturally processed peptides selected by antigen-presenting cells homozygous for expression of I-A(g7) or I-A(d) class II MHC molecules, or from heterozygous antigen-presenting cells that express I-A(g7) along with I-A(g7PD) or I-A(d). Identification of large numbers of peptides demonstrated that despite being closely related on a structural level, each class II MHC molecule selected for very unique peptides. The large data sets allowed us to definitively establish the preferred peptide-binding motifs critical for selection of peptides by I-A(g7), I-A(g7PD), and I-A(d). Finally, extensive analyses of peptide families reveals that there was little competition among class II MHC alleles for display of peptides and that presence of one allele had minimal impact on the repertoire of peptides selected by another.