Allele-specific differences in the interaction of MHC class I molecules with transporters associated with antigen processing.
MHC class I molecules bind peptides that are translocated from the cytosol into the endoplasmic reticulum by the peptide transporter associated with antigen processing (TAP). Class I heterodimers have been shown to associate with TAP and are released when loaded with peptide. Here, we show the existence of two pools of class I heterodimers, one associated with TAP and one that is free. Whereas the free pool is recognized by the class I-specific Ab W6/32, the TAP-associated pool is not. Analysis of several class I alleles shows binding to TAP with different efficiencies, even at the earliest time points of MHC class I assembly. Most HLA-A and -C alleles tested interacted efficiently with TAP, whereas a considerable number of HLA-B alleles associated very inefficiently or not at all with TAP. This was also observed in cells with nonfunctional TAP. Sequence comparison of the different class I alleles allowed the definition of amino acids in the peptide binding groove that might be involved in TAP association. Binding of peptides to two different pools of class I heterodimers may ensure efficient peptide association in an environment where peptides have a short life span.
Neisig
A
A
Department of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
Wubbolts
R
R
Zang
X
X
Melief
C
C
Neefjes
J
J
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D001692:Biological Transport / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011817:Rabbits
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human