title: CDR3 motif generation and selection in the BV19-utilizing subset of the human CD8 T cell repertoire.
abstract: The amino acids at the V-J rearrangement junction of TCR are encoded by the D region and by N or P nucleotides. Together they comprise the NDN region, the specific pMHC selection surface of the TCR β-chain. As an extension of our earlier work on the recall response to influenza M158-66 in HLA-A2 individuals, we have been analyzing the circulating BV19 CD8 T cell repertoires. We observed that NDN regions of the CDR3 often start at positions that are V-region encoded. Here we examine NDN encoded amino acid motifs of BV19 rearrangements in circulating CD8 T cells based on the CDR3 length, the CDR3 start position of the NDN, and the motif length. Motifs that start at V region-encoded positions could be expected to be CDR3 length independent as indeed is the case. Motifs that included sequential proline and glycine showed a CDR3 length independent distribution and examining codon usage indicates that a large proportion of these can be explained by P-nucleotide addition from the 5' end of the D region. Other examples of skewed codon usage were observed indicating possible additional rearrangement mechanisms. Another pattern of motif distributions was a shift of position along the CDR3 as a function of the CDR3 length. As these data were collected from an older healthy individual they can be used to model successful repertoire selection and to further define characteristics associated with a positive history of responses to pathogen exposures.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, United States.
authors.forename: Maryam B
authors.initials: MB
authors.lastname: Yassai
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, United States.
authors.forename: Wendy
authors.initials: W
authors.lastname: Demos
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, United States. Electronic address: Jack.Gorski@bcw.edu.
authors.forename: Jack
authors.initials: J
authors.lastname: Gorski
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003062:Codon; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007156:Immunologic Memory; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D003062:Codon; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: CDR3 amino acid motifs; NDN rearrangement patterns; P nucleotide addition; TCR beta