Characterization of Human CD8αβ Interaction With Classical and Unconventional MHC Molecules.

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Ben de Wet, Robert Alan Simmons, Richard J Suckling, Rita Szoke-Kovacs, Salah Mansour, Marco Lepore, David K Cole, Jakub Jaworski, Alexandra L Chapman, Milos Aleksic
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引用次数: 0

Abstract

The CD8 co-receptor exists as both an αα homodimer, expressed on subsets of specialized lymphoid cells, and as an αβ heterodimer, which is the canonical co-receptor on cytotoxic T-cells, tuning TCR thymic selection and antigen-reactivity in the periphery. However, the biophysical parameters governing human CD8αβ interactions with classical MHC class I (MHCI) and unconventional MHC-like molecules have not been determined. Using hetero-dimerized Fc-fusions to generate soluble human CD8αβ, we demonstrate similar weak binding affinity to multiple different MHCI alleles compared with CD8αα. We observed that both forms of CD8 bound to certain alleles with stronger affinity than others and found that the affinity of thymically selected TCRs was inversely associated with the affinity of the CD8 co-receptor for the different alleles. We further demonstrated the binding of CD8αα and CD8αβ to the unconventional MHC-like molecule, MHCI-related protein 1, with a similar affinity as for classical MHCI, but no interaction was observed for the other unconventional MHC-like molecules, CD1a, b, c, or d. In summary, this is the first characterization of human CD8αβ binding to MHCI and MHC-like molecules that revealed an intriguing relationship between CD8 binding affinity for different MHCI alleles and the selection of TCRs in the thymus.

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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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