期刊
IMMUNOLOGY
卷 113, 期 4, 页码 460-471出版社
WILEY
DOI: 10.1111/j.1365-2567.2004.01985.x
关键词
antigen presentation; ICAM-1; membrane rafts; MHC class I; target cells
类别
资金
- NCI NIH HHS [5-T32-CA09683, T32 CA009683] Funding Source: Medline
- NIAID NIH HHS [AI39966, 5-T32-AI07523, R01 AI039966, AI3254, T32 AI007523] Funding Source: Medline
- NIGMS NIH HHS [GM-28526, R01 GM028526] Funding Source: Medline
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 Ca2+ 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.
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