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Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503

  1. Author:
    Thammavongsa, V.
    Schaefer, M.
    Filzen, T.
    Collins, K. L.
    Carrington, M.
    Bangia, N.
    Raghavan, M.

  2. Author Address

    [Filzen, Tracey; Collins, Kathleen L.; Raghavan, Malini] Univ Michigan, Dept Microbiol & Immunol, Sch Med, Ann Arbor, MI 48109 USA. [Thammavongsa, Vilasack; Schaefer, Malinda] Univ Michigan, Grad Program Immunol, Sch Med, Ann Arbor, MI 48109 USA. [Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21702 USA. [Bangia, Naveen] Roswell Pk Canc Inst, Dept Immunol, CCC, Buffalo, NY 14263 USA.;Raghavan, M, Univ Michigan, Dept Microbiol & Immunol, Sch Med, 5641 Med Sci Bldg 2, Ann Arbor, MI 48109 USA.;malinir@umich.edu
    1. Year: 2009
    2. Date: Dec
  2. Journal: Immunogenetics
    1. 61
    2. 11-12
    3. Pages: 703-716
  4. Type of Article: Article
  5. ISSN: 0093-7711
  1. Abstract:

    Residue 116 of major histocompatibility complex (MHC) class I heavy chains is an important determinant of assembly, that can influence rates of ER-Golgi trafficking, binding to the transporter associated with antigen processing (TAP), tapasin dependence of assembly, and the efficiency and specificity of peptide binding. Here, we investigated assembly and peptide-binding differences between HLA-B*3501(S116) and HLA-B*3503(F116), two alleles differing only at position 116 of the MHC class I heavy chain, that are associated respectively with normal or rapid AIDS progression. A reduced intracellular maturation rate was observed for HLA-B*3503 in HIV-infected and uninfected cells, which correlated with enhanced binding of HLA-B*3503 to TAP. No significant differences in the intrinsic efficiency of in vitro peptide binding by HLA-B*3501 and HLA-B*3503 were measurable with several common peptides or peptide libraries, and both allotypes were relatively tapasin-independent for their assembly. However, thermostability differences between the two allotypes were measurable in a CD4(+) T cell line. These findings suggest that compared to HLA-B*3501, a reduced intracellular peptide repertoire for HLA-B*3503 could contribute to its slower intracellular trafficking and stronger association with rapid AIDS progression.

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External Sources

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  2. DOI: 10.1007/s00251-009-0399-2
  3. View record in Web of Science®
  4. WOS: 000273359700001

Library Notes

  1. Fiscal Year: FY2009-2010
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