title: Direct binding of the MHC class I molecule H-2Ld to CD8: interaction with the amino terminus of a mature cell surface protein.
abstract: MHC class I molecules (MHC-I) display peptides from the intracellular pool at the cell surface for recognition by T lymphocytes bearing alphabeta TCR. Although the activation of T cells is controlled by the interaction of the TCR with MHC/peptide complexes, the degree and extent of the activation is influenced by the binding in parallel of the CD8 coreceptor with MHC-I. In the course of quantitative evaluation of the binding of purified MHC-I to engineered CD8, we observed that peptide-deficient H-2Ld (MHC-I) molecules bound with moderate affinity (Kd = 7.96 x 10(-7) M), but in the presence of H-2Ld-binding peptides, no interaction was observed. Examination of the amino terminal sequences of CD8alpha and beta chains suggested that H-2Ld might bind these protein termini via its peptide binding cleft. Using both competition and real-time direct assays based on surface plasmon resonance, we detected binding of empty H-2Ld to synthetic peptides representing these termini. These results suggest that some MHC molecules are capable of binding the amino termini of intact cell surface proteins through their binding groove and provide alternative explanations for the observed binding of MHC molecules to a variety of cell surface receptors and coreceptors.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Jelonek
authors.forename: B J
authors.initials: BJ
authors.lastname: Classon
authors.forename: P J
authors.initials: PJ
authors.lastname: Hudson
authors.forename: D H
authors.initials: DH
authors.lastname: Margulies
mesh_terms: D000818:Animals; D001665:Binding Sites; D016827:CD8 Antigens / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D006183:H-2 Antigens / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice
chemical_list: D016827:CD8 Antigens; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008565:Membrane Proteins