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A strategy to determine HLA class II restriction broadly covering the DR, DP, and DQ allelic variants most commonly expressed in the general population

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Abstract

Classic ways to determine MHC restriction involve inhibition with locus-specific antibodies and antigen presentation assays with panels of cell lines matched or mismatched at the various loci of interest. However, these determinations are often complicated by T cell epitope degeneracy and promiscuity. We describe a selection of 46 HLA DR, DQ, and DP specificities that provide worldwide population (phenotypic) coverage of almost 90 % at each locus, and account for over 66 % of all genes at each locus. This panel afforded coverage of at least four HLA class II alleles in over 95 % of the individuals in four study populations of diverse ethnicity from the USA and South Africa. Next, a panel of single HLA class II-transfected cell lines, corresponding to these 46 allelic variants was assembled, consisting of lines previously developed and 15 novel lines generated for the present study. The novel lines were validated by assessing their HLA class II expression by FACS analysis, the in vitro peptide binding activity of HLA molecules purified from the cell lines, and their antigen presenting capacity to T cell lines of known restriction. We also show that these HLA class II-transfected cell lines can be used to rapidly and unambiguously determine HLA restriction of epitopes recognized by an individual donor in a single experiment. This panel of lines will enable high throughput determination of HLA restriction, enabling better characterization of HLA class II-restricted T cell responses and facilitating the development of HLA tetrameric staining reagents.

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Acknowledgments

We thank Victoria Tripple, Duy Le, and Ryan Henderson for the technical assistance. We thank Dr. Robert Karr for providing us with a large panel of single transfected HLA class II cell lines, and Dr. Karr and Dr. Howard Grey for their helpful comments. This work was supported by National Institutes of Health contract no. N01-AI-900044C, AI-900048C, AI-100275 (to A.S.) and Bill and Melinda Gates Foundation grant OPP1021972-3 (to W.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

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Authors and Affiliations

  1. La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, San Diego, CA, 92037, USA

    Denise M. McKinney, Scott Southwood, Denise Hinz, Carla Oseroff, Cecilia S. Lindestam Arlehamn, Veronique Schulten, Bjoern Peters, John Sidney & Alessandro Sette

  2. University of California, La Jolla, San Diego, CA, 92037, USA

    Randy Taplitz & David Broide

  3. South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

    Willem A. Hanekom & Thomas J. Scriba

  4. The Johns Hopkins University, Baltimore, MD, 21201, USA

    Robert Wood

  5. National Jewish Health, Denver, CO, 80206, USA

    Rafeul Alam

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  1. Denise M. McKinney
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Correspondence to Alessandro Sette.

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McKinney, D.M., Southwood, S., Hinz, D. et al. A strategy to determine HLA class II restriction broadly covering the DR, DP, and DQ allelic variants most commonly expressed in the general population. Immunogenetics 65, 357–370 (2013). https://doi.org/10.1007/s00251-013-0684-y

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