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Domain‐specific CD 6 monoclonal antibodies identify CD 6 isoforms generated by alternative‐splicing
Author(s) -
Santos Rita F.,
Oliveira Liliana,
Brown Marion H.,
Carmo Alexandre M.
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13087
Subject(s) - ectodomain , gene isoform , alternative splicing , monoclonal antibody , scavenger receptor , biology , microbiology and biotechnology , rna splicing , glycoprotein , transmembrane domain , receptor , transmembrane protein , biochemistry , chemistry , antibody , gene , rna , genetics , lipoprotein , cholesterol
Summary The characterization of the architecture, structure and extracellular interactions of the CD 6 glycoprotein, a transmembrane receptor expressed in medullary thymocytes and all mature T‐cell populations, has been enhanced by the existence of monoclonal antibodies ( mA bs) that specifically recognize the various scavenger receptor cysteine‐rich ( SRCR ) domains of the ectodomain. Using engineered isoforms of CD 6 including or excluding each of the three SRCR domains, either expressed at the membranes of cells or in soluble forms, we provide conclusive and definitive evidence that domain 2 of CD 6, previously not identifiable, can be recognized by the CD 6 mA bs OX 125 and OX 126, and that OX 124 targets domain 3 and can block the interaction at the cell surface of CD 6 with its major ligand CD 166. Alternative splicing‐dependent CD 6 isoforms can now be confidently identified. We confirm that following T‐cell activation there is a partial replacement of full‐length CD 6 by the CD 6Δd3 isoform, which lacks the CD 166‐binding domain, and we find no evidence for the expression of other CD 6 isoforms at the mRNA or protein levels.