Kulig, Kimary and Nandi, Dipankar and Bacík, Igor and Monaco, John J and Vukmanovic, Stanislav (1998) Physical and functional association of the major histocompatibility complex class I heavy chain alpha 3 domain with the transporter associated with antigen processing. In: Journalof Experemental Medicine, 187 (06). pp. 865-874.
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CD8(+) T lymphocytes recognize antigens as short, MHC class I-associated peptides derived by processing of cytoplasmic proteins. The transporter associated with antigen processing translocates peptides from the cytosol into the ER lumen, where they bind to the nascent class I molecules. To date, the precise location of the class I-TAP interaction site remains unclear. We provide evidence that this site is contained within the heavy chain alpha 3 domain. Substitution of a 15 amino acid portion of the H-2D(b) alpha 3 domain (aa 219-233) with the analogous MHC class II (H-2IA(d)) beta 2 domain region (aa 133-147) results in loss of surface expression which can be partially restored upon incubation at 26 degrees C in the presence of excess peptide and beta 2-microglobulin. Mutant H-2D(b) (D(b)219-233) associates poorly with the TAP complex, and cannot present endogenously-derived antigenic peptides requiring TAP-dependent translocation to the ER. However, this presentation defect can be overcome through use of an ER targeting sequence which bypasses TAP-dependent peptide translocation. Thus, the alpha 3 domain serves as an important site of interaction (directly or-indirectly) with the TAP complex and is necessary for TAP-dependent peptide loading and class I surface expression.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to Rockefeller University Press.|
|Department/Centre:||Division of Biological Sciences > Biochemistry|
|Date Deposited:||29 Dec 2009 09:02|
|Last Modified:||19 Sep 2010 05:26|
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