Interactions of HLA-B*4801 with peptide and CD8.
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 CD8 alpha homodimers weakly due to the presence of a threonine residue at position 245 in the alpha 3 domain. A mutant B*4801 molecule in which alanine replaces threonine 245, binds CD8 alpha homodimers at levels comparable to those of other HLA class I allotypes. Despite the low affinity of B*4801 for CD8 alpha, 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.
Martinez-Naves
E
E
Department of Structural Biology and Microbiology & Immunology, Stanford University School of Medicine, California, USA.
Barber
L D
LD
Madrigal
J A
JA
Vullo
C M
CM
Clayberger
C
C
Lyu
S C
SC
Williams
R C
RC
Gorodezky
C
C
Markow
T
T
Petzl-Erler
M L
ML
Parham
P
P
D000483:Alleles; D016827:CD8 Antigens / Q000378:metabolism*; D002460:Cell Line; D015235:HLA-B Antigens / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D016827:CD8 Antigens; D015235:HLA-B Antigens