Cancer Vaccines Clinical Applications Peptides and Protein英文电子书.pdf

18.3: Cancer Vaccines: Clinical Applications: Peptides and Protein Vaccines Peptide Presentation on Major Histocompatibility Complex Molecules The T-cell receptor on lymphocytes with antitumor activity recognize a unique conformation on the tumor cell surface comprised of a peptide nestled in the groove of a surface major + histocompatibility complex (MHC) molecule (1,2). CD8 T cells recognize peptides attached to class I molecules, and CD4 cells recognize peptides attached to class II molecules. Class I MHC molecules consist of a heavy chain of 45,000 d and a noncovalently attached beta-2- microglobulin of 12,000 d. There are three major HLA class I alleles called HLA-A, -B, and -C. Class II molecules are heterodimers consisting of an alpha and beta chain of approximately 30,000 d each, and the three class II alleles are called HLA-DR, -DQ, and -DP. X-ray diffraction crystallography has characterized the three-dimensional structure of class I and II molecules and their peptide-binding sites. The cellular processes resulting in the binding of peptides to class I and II molecules are different. The great majority of class I–presented peptides result from the degradation of cytosolic proteins by a multi-unit structure in the cytoplasm called the proteosome. Cleaved peptides are transported into the lumen of the endoplasmic reticulum (ER) by the transporter associated with processing molecule, possibly protected from complete degradation by chaperone heat-shock proteins before entering the ER. The trimmed peptides are bound to the groove of the assembled class I molecule in the ER, and the complex is transported to the cell surface. Most peptides that are loaded onto class II molecules are derived from proteins that are endocytosed into the cell and are degraded in intracellular compartments in endosomal or lysosomal structures