Chicken T-cell receptor beta-chain diversity: an evolutionarily conserved D beta-encoded glycine turn within the hypervariable CDR3 domain.

Abstract

(6,7). After rearrangement, the VH and VL segments undergo sequence diversification by intrachromosomal gene conversion using families of V pseudogene segments as sequence donors (6-10). Given these differences between mammalian and avian Ig gene diversification, it was of interest to determine the molecular mechanisms for the diversification of chicken We have examined the molecular mechanisms for the generation of diversity in the chicken TCRE locus by identifying the germ-line chicken Do gene segment and by analyzing rearranged chicken TCRJ3 genes isolated from the developing thymus and mature spleen.t We observe that chicken TCR,8 diversity is generated by junctional variability, rather than by gene conversion, as in chicken Ig genes. Further, the junctional diversity increases during development due to increased random base-pair (N-nucleotide) addition. Within the junctional variability, however, most rearranged chicken TCR,8 genes have at least one glycine residue, which is encoded in the germ-line by an evolutionarily conserved Do segment. The implications of a conserved glycine for TCR structure and antigen recognition are discussed.

Evolution of Antigen Binding Receptors

“…Four Jβ segments and a single Cβ element were identified. The extent of N-region addition increases during development and is consistent with ontogenetic up-regulation of terminal deoxynucleotide transferase (TdT) in the thymus (137). The chicken Dβ region encodes a glycine residue in all three reading frames that presumably participates in the formation of a CDR3-encoded loop structure (137).…”

T-cell receptor gene homologs are present in the most primitive jawed vertebrates.

“…From the sequence shown in Fig. 1 and by analogy to higher vertebrate TCR (3-chain genes, it is reasonable to assume that a D segment(s), possessing 12-nucleotide 5' and 23-nucleotide 3' recombination signal sequences, may be present between VT and JT (7,32) in addition to junctional insertion of nucleotide sequence (Fig. 4B); alternatively, direct V-J joining may occur.…”

“…TCR function involves recognition of antigenic peptides bound to major histocompatibility complex (MHC) class I or II molecules (2) and diversity is achieved by many, but not all, of the mechanisms used in generating B-cell immunity (4,5). Understanding the evolution ofTCRs largely has been limited to interpretation of findings regarding gene structure and organization in several mammalian, an avian (6)(7)(8), and an amphibian (9) species. Although TCR genes have not yet been identified in bony fish, their existence is suggested by the presence of distinct T-cell functions (10,11) and both MHC 1 (12) and MHC II (12,13) genes.…”

Intestinal CD8αα and CD8αβ Intraepithelial Lymphocytes Are Thymus Derived and Exhibit Subtle Differences in TCRβ Repertoires

“…The TCR␤ rearrangement can start either by the V␤1D␤ or the D␤J␤ step and is restricted to the thymus at least during embryogenesis (25). Because of its relatively small heterogeneity among germline V, D, and J␤ elements, TCR␤ diversity is largely maintained by the variable N nucleotide addition at the coding joints of VD and DJ recombinations (16,19,20).…”

“…The variable TCR ␤-chain comprises the two major gene families V␤1 and V␤2, and T cells expressing either of these genes differ in their ontogeny and function (19,20). V␤2 T cells appear later in the thymus and periphery than V␤1 T cells and infrequently migrate to the intestine; the two subsets also differ in their graft-vs-host reaction capacity (18,23).…”