Peptide Translocation by Variants of the Transporter Associated with Antigen Processing

• Published in: Science (American Association for the Advancement of Science) Vol. 262; no. 5142; pp. 2059 - 2063
• Main Authors: Heemels, Marie-Thérèse, Ton N. M. Schumacher, Wonigeit, Kurt, Ploegh, Hidde L.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 24.12.1993; American Association for the Advancement of Science
• Subjects: Alleles; Amino Acid Sequence; Animals; Antigen presentation; Antigen Presentation - physiology; Antigen-antibody reactions, antigen-antibody complexes, antibody-complement and others. Study of affinity. Antigen presentation; ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP Binding Cassette Transporter, Subfamily B, Member 3; ATP-Binding Cassette Transporters; Biological and medical sciences; Biological Transport - physiology; Carrier Proteins - genetics; Carrier Proteins - physiology; Elution; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gels; Histocompatibility Antigens Class I - physiology; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - physiology; In Vitro Techniques; Libraries; Liver microsomes; Major histocompatibility complex; Microsomes; Microsomes, Liver - metabolism; Molecular immunology; Molecular Sequence Data; Molecules; Oligopeptides - metabolism; Peptide regulatory factors; Peptides; Physiological aspects; Radioactive decay; Rats; Rats, Inbred BN; Rats, Inbred Lew; Rats, Inbred SHR; Substrate Specificity; Translocation; Antigen presentation; Intracellular transport; Molecular processing; Peptides; Rat; Major histocompatibility system; Biological transport; Rodentia; Microsome; Vertebrata; Mammalia; Class I histocompatibility antigen
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8266106

Major histocompatibility complex (MHC) class I molecules associate with peptides that are delivered from the cytosol to the lumen of the endoplasmic reticulum by the transporter associated with antigen processing (TAP). Liver microsomes of SHR and Lewis rats, which express different alleles of TAP (cim$^b$ and cim$^a$, respectively), accumulate different sets of peptides. Use of MHC congenic rats assigned this difference to the MHC, independent of the class I products expressed. Both the cim$^a$ and cim$^b$ TAP complexes translocate peptides with a hydrophobic carboxyl terminus, but translocation of peptides with a carboxyl-terminal His, Lys, or Arg residue is unique to cim$^a$. Thus, the specificity of the TAP peptide translocator restricts the peptides available for antigen presentation.