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The Journal of Immunology, Vol 156, Issue 9 3196-3206, Copyright © 1996 by American Association of Immunologists


ARTICLES

Allele-specific differences in the interaction of MHC class I molecules with transporters associated with antigen processing

A Neisig, R Wubbolts, X Zang, C Melief and J Neefjes
Department of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.

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.


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