[HLA-peptide complex and immunity-related diseases]

The class II HLA molecule (HLA-DR, -DQ or -DP) is expressed on various antigen presenting cells (APC). Proteolytic fragments of peptides processed by APC that match the physiochemical character of the peptide-binding grooves formed by alpha and beta chains of class II HLA molecules are expressed on the surface of APC and are recognized by T cells. Many class II-binding peptide motifs reported to date follow the 9-mer peptide pattern AxxBxCDxE, with A, B, C, D, and E residues functioning to bind to HLA, thereby designated as "anchors". On the contrary, the x residues are recognized by T cells through the T cell receptor (TCR). Analog peptides with single residue substitutions at x residues changed signals in T cells, leading to quantitative and qualitative (anergy/survival, etc.) changes in human T cell clonal responses. Certain analogs changed signals in monocytes, leading to the upregulation of IL-12. Furthermore, cross-linking of class II HLA molecules on monocytes using mAbs leads to upregulation of monokines, in which HLA-DR, -DQ, and -DP play differential roles. Thus, HLA molecules when recognized by TCR, not only present peptide antigens to T cells but also transmit signals to APC, where the polymorphism and heterogeneity of HLA molecules may play important roles.