title: Major histocompatibility complex class I-intercellular adhesion molecule-1 association on the surface of target cells: implications for antigen presentation to cytotoxic T lymphocytes.
abstract: Polarization and segregation of the T-cell receptor (TCR) and integrins upon productive cytotoxic T-lymphocyte (CTL) target cell encounters are well documented. Much less is known about the redistribution of major histocompatibility complex class I (MHC-I) and intercellular adhesion molecule-1 (ICAM-1) proteins on target cells interacting with CTLs. Here we show that human leucocyte antigen-A2 (HLA-A2) MHC-I and ICAM-1 are physically associated and recovered from both the raft fraction and the fraction of soluble membranes of target cells. Conjugation of target cells with surrogate CTLs, i.e. polystyrene beads loaded with antibodies specific for HLA-A2 and ICAM-1, induced the accumulation of membrane rafts, and beads loaded with ICAM-1-specific antibodies caused the selective recruitment of HLA-A2 MHC-I at the contact area of the target cells. Disruption of raft integrity on target cells led to a release of HLA-A2 and ICAM-1 from the raft fraction, abatement of HLA-A2 polarization, and diminished the ability of target cells bearing viral peptides to induce a Ca(2+) flux in virus-specific CTLs. These data suggest that productive engagement of ICAM-1 on target cells facilitates the polarization of MHC-I at the CTL-target cell interface, augmenting presentation of cognate peptide-MHC (pMHC) complexes to CTLs. We propose that ICAM-1-MHC-I association on the cell membrane is a mechanism that enhances the linkage between antigen recognition and early immunological synapse formation.
authors.affiliation: Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lebedeva
authors.forename: Nadja
authors.initials: N
authors.lastname: Anikeeva
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Ibragim
authors.initials: I
authors.lastname: Gaidarov
authors.forename: James H
authors.initials: JH
authors.lastname: Keen
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sykulev
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D021962:Membrane Microdomains / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D047392:beta-Cyclodextrins / Q000494:pharmacology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D004791:Enzyme Inhibitors; D015789:HLA-A2 Antigen; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D018799:Intercellular Adhesion Molecule-1; D019061:src-Family Kinases; D002118:Calcium