Human CD6 Possesses a Large, Alternatively Spliced Cytoplasmic Domain

Eur J Immunol. 1995 Oct;25(10):2765-9. doi: 10.1002/eji.1830251008.


Human CD6 is a monomeric 105/130-kDa T cell surface glycoprotein that is involved in T cell activation. The apparent discrepancy between the size of the cytoplasmic domain in human (44 amino acids) and mouse (243 amino acids) CD6, led us to use reverse transcriptase-polymerase chain reaction of human peripheral blood lymphocyte mRNA to isolate cDNA clones that include the carboxyl-terminal coding region of human CD6. The nucleotide sequence of the longest human cDNA clone, CD6-PB1, predicts a protein of 668 amino acids with a 244-amino acid cytoplasmic domain similar in size to and possessing 71.5% amino acid sequence identity with the cytoplasmic domain of mouse CD6. This previously unrecognized 244-amino acid cytoplasmic domain does not have significant homology to any other known protein (except mouse CD6), but does possess two proline-rich motifs containing the SH3 domain-binding consensus sequence, a serine-threonine-rich motif repeated three times, three protein kinase C phosphorylation-site motifs, and 10 casein kinase-2 phosphorylation-site motifs. These sequences are likely to play a role in the ability of CD6-specific monoclonal antibodies to stimulate T cell proliferation. Full-length CD6 cDNA containing this cytoplasmic domain sequence encodes a monomeric 105/130-kDa protein that can be immunoprecipitated from the surface of transfected cells and comigrates upon SDS-PAGE with wild-type CD6 immunoprecipitated from PBL. We also isolated two alternatively spliced forms of human CD6 cDNA lacking sequences encoding membrane-proximal regions of the cytoplasmic domain which maintain the same reading frame as CD6-PB1. The short cytoplasmic domain of the previously reported human CD6-15 cDNA clone results from a deletion of a 20-bp segment through use of an alternative 3' splice site, resulting in a frame shift and premature termination of translation relative to the clones we have isolated. These data demonstrate that human CD6 possesses a large cytoplasmic domain containing sequence motifs that are likely to be involved in signal transduction upon stimulation of T cells through CD6 ligation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD / chemistry*
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / chemistry*
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Base Sequence
  • DNA, Complementary / genetics
  • Humans
  • L Cells
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Protein Structure, Tertiary*
  • RNA Splicing*
  • Sequence Alignment
  • Signal Transduction
  • Species Specificity
  • T-Lymphocytes / immunology
  • Transfection
  • src Homology Domains


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD6 antigen
  • DNA, Complementary

Associated data

  • GENBANK/U34623
  • GENBANK/U34624
  • GENBANK/U34625