Interactions of HLA-B*4801 with peptide and CD8 |
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| Authors: | E Martinez-Naves LD Barber JA Madrigal CM Vullo C Clayberger S-C Lyu RC Williams C Gorodezky T Markow ML Petzl-Erler P Parham |
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| Institution: | Departments of Structural Biology and Microbiology &Immunology, Stanford University School of Medicine, Stanford, California, USA;Departments of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California, USA;Laboratorio de Histocompatibilidad, Hospital Nacional de Clínicas, Córdoba National University, Córdoba, Argentina;Department of Immunogenetics, INORE, SSA, Mexico D.F., Mexico;Departments of Anthropology, Arizona State University, Tempe, USA;Departments of Zoology, Arizona State University, Tempe, USA;Department of Genetics, Federal University of Paraná, Brazil |
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| Abstract: | Functional properties of the B*4801 allotype were investigated using HLA class I-deficient 221 cells transfected with B*4801 cDNA. From pool sequence analysis of endogenously bound peptides, B*4801 was shown to select for nonamer peptides having glutamine or lysine at position 2 and leucine at the carboxyl-terminus. In an in vitro cell-cell binding assay, B*4801 binds CD8α homodimers weakly due to the presence of a threonine residue at position 245 in the α3 domain. A mutant B*4801 molecule in which alanine replaces threonine 245, binds CD8α homodimers at levels comparable to those of other HLA class I allotypes. Despite the low affinity of B*4801 for CD8α, alloreactive T-cells that recognize B*4801 molecules expressed by the 221 transfectant are inhibited by anti-CD8 monoclonal antibodies. Analysis of 25 B*48-expressing individuals from various populations showed threonine 245 was encoded by every B*48 allele. |
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| Keywords: | Amerindian B*4801 CD8 HLA class I peptide-binding |
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