The delta T cell receptor repertoire in human colon and peripheral blood is oligoclonal irrespective of V region usage.

Holtmeier, Wolfgang; Chowers, Yehuda; Lumeng, Amy; Morzycka-Wroblewska, Ewa; Kagnoff, Martin F.

doi:10.1172/jci118097

Cited by 60 publications

(50 citation statements)

References 63 publications

(79 reference statements)

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“…The marked complexity of the TCR junctional sequences and oligoclonality of the TCR repertoire in the twins was typical of that reported by us and others in healthy adults, and appears to reflect positive selection and expansion of specific populations of T cells [24,33,44,45]. However, in contrast to healthy individuals, in whom the TCR repertoire is relatively compartmentalized with little overlap between the small intestine and colon ( [33] and W. Holtmeier, unpublished data), we note there was marked overlap between the TCR repertoire in the small intestine and sigmoid colon of each twin.…”

Section: Discussionsupporting

confidence: 79%

“…5, the V 1, V 2 and V 3 transcripts were all in frame. Junctional regions of the transcripts were complex, as shown by extensive nucleotide insertions and deletions at the junctions of V, D and J gene segments, and the extent of this complexity was comparable to that reported before in healthy adults [24,33]. Although DJ1 (J 1) was the predominant TCRDJ segment used, DJ2 or DJ3 segments were used by several V 1 and V 2 transcripts with long CDR3 domains.…”

Section: Translation Of Nucleotide Sequences From Tcr V 1 V 2 and V supporting

confidence: 80%

“…Lengths of the CDR3 domains of translated TCR transcripts were determined as described before [24,41]. Briefly, the distance was calculated between the conserved cysteine at position 88, which is encoded by the 3 0 TCRDV region, and the conserved GXG triplet, which is encoded by all TCRDJ regions, and eight amino acids were subtracted [41][42][43].…”

Section: Cdr3 Lengthmentioning

confidence: 99%

“…Most / IEL utilize the TCRDV1 [23] gene segment [10,14,24], while fewer cells express TCRDV2, TCRDV3 and TCRAV gene segments [24][25][26]. In contrast, most / T cells in the circulation express the TCRDV2 gene segment [27,28].…”

Section: Introductionmentioning

confidence: 99%

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Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Holtmeier

Rowell

Nyberg

et al. 1997

Clinical and Experimental Immunology

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SUMMARYOne of the hallmarks of coeliac disease, both active and treated, is an increased number and proportion of°/± intraepithelial T lymphocytes in the small intestinal mucosa, and an increased number of°/± T cells in the small intestinal mucosa of coeliac disease patients has been associated with the inheritance of specific HLA class II DQ alleles. Nonetheless, the contribution of genetic factors to the development of the T cell receptor (TCR) ± repertoire in coeliac disease is not known. We have assessed the contribution of genetic factors to development of the TCR ± repertoire in coeliac disease, by characterizing the junctional diversity of TCR ± transcripts expressed in the intestine and peripheral blood of a pair of monozygotic (MZ) twins concordant for coeliac disease. TCR V±1, V±2 and V±3 transcripts from small intestinal and colon biopsies, and from peripheral blood mononuclear cells, were amplified by polymerase chain reaction (PCR) and the complementarity determining region (CDR)3 domains of TCR ± transcripts were analysed by denaturing PAGE and direct nucleotide sequencing. The repertoire of TCR ± transcripts and CDR3 amino acid motifs in the intestine and peripheral blood of MZ twins concordant for coeliac disease exhibited no overlap. The TCR ± repertoire in each twin was oligoclonal, and complexity of the junctional regions of their TCR ± transcripts was typical of the repertoire in healthy adults. Thus, genetically identical individuals with coeliac disease have distinct, non-overlapping TCR ± repertoires. Moreover, genetic factors that determine disease susceptibility do not appear to select for specific TCR ± sequences or CDR3 amino acid motifs. Keywords ±T cell receptor coeliac disease monozygotic twins T cell receptor repertoire°/

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Section: Discussionsupporting

confidence: 79%

Section: Translation Of Nucleotide Sequences From Tcr V 1 V 2 and V supporting

confidence: 80%

Section: Cdr3 Lengthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Holtmeier

Rowell

Nyberg

et al. 1997

Clinical and Experimental Immunology

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“…Together with our previous studies in humans [29,[45][46][47] and reports of studies on nonhuman primates [71,87] a general paradigm emerges in which in each organ, different antigens select and maintain the γδ TR repertoire. The homogenous distribution of dominant γδ T cell clones along the small or large intestine is most likely the result of γδ T cells that are selected by ligands in the intestinal tract and undergo expansion and recirculation before lodging throughout the small or large intestine.…”

Section: The Porcine Tr V Delta (Trdv) Repertoirementioning

confidence: 53%

Development of the neonatal B and T cell repertoire in swine: implications for comparative and veterinary immunology

et al. 2006

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-Birth in all higher vertebrates is at the center of the critical window of development in which newborns transition from dependence on innate immunity to dependence on their own adaptive immunity, with passive maternal immunity bridging this transition. Therefore we have studied immunological development through fetal and early neonatal life. In swine, B cells appear earlier in fetal development than T cells. B cell development begins in the yolk sac at the 20th day of gestation (DG20), progresses to fetal liver at DG30 and after DG45 continues in bone marrow. The first wave of developing T cells is γδ cells expressing a monomorphic Vδ rearrangement. Thereafter, αβ T cells predominate and at birth, at least 19 TRBV subgroups are expressed, 17 of which appear highly homologous with those in humans. In contrast to the T cell repertoire and unlike humans and mice, the porcine pre-immune VH (IGHV-D-J) repertoire is highly restricted, depending primarily on CDR3 for diversity. The V-KAPPA (IGKV-J) repertoire and apparently also the V-LAMBDA (IGLV-J) repertoire, are also restricted. Diversification of the pre-immune B cell repertoire of swine and the ability to respond to both T-dependent and T-independent antigen depends on colonization of the gut after birth in which colonizing bacteria stimulate with Toll-like receptor ligands, especially bacterial DNA. This may explain the link between repertoire diversification and the anatomical location of primary lymphoid tissue like the ileal Peyers patches. Improper development of adaptive immunity can be caused by infectious agents like the porcine reproductive and respiratory syndrome virus that causes immune dysregulation resulting in immunological injury and autoimmunity.

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Expansion of circulating Vγ9 / Vδ1 T cells in a patient with a syndrome of recurrent fever: evidence for an unusual antigen-driven process leading to selection of recurrent motifs within TCR junctional loops of diverse lengths

et al. 1999

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Polyclonal expansions of human Vδ1 T cells have been described in diverse physiopathological situations without strong TCR structural data for an antigen‐driven selection. Here, we have analyzed the phenotype and TCR repertoire of γ δ T cells obtained from the peripheral blood of a 19‐year‐old patient with a syndrome of recurrent fever, which accounted for up to 40 % of CD3+ T cells and expressed predominantly Vγ9 and Vδ1 TCR regions and a memory phenotype. Sequence analysis of Vδ1‐Jδ1 transcripts derived from peripheral blood lymphocytes (PBL) indicated that, while Vδ1‐Jδ1 junctional sequences were diverse in length, all but one contained several recurrent motifs at conserved positions from both the 5′‐ and 3′‐ends of the complementarity‐determining region (CDR)3 loop. Analysis of γ δ T cell clones derived from patient PBL demonstrated that Vγ9+ but not Vγ9– T cell clones frequently expressed Vδ1 chains with these characteristics and unveiled a hierarchy between the constraints imposed on the 5′‐ vs. the 3′ motifs of the Vδ1 CDR3 loops. These results constitute the first strong evidence for a nominal antigen‐driven selection of Vδ1 T cells in vivo and also suggest that the hierarchy of the constraints imposed by antigens respectively on the length and amino acid composition of TCR CDR3 loops differs between α β and γ δ T cells.

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The delta T cell receptor repertoire in human colon and peripheral blood is oligoclonal irrespective of V region usage.

Cited by 60 publications

References 63 publications

Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Development of the neonatal B and T cell repertoire in swine: implications for comparative and veterinary immunology

Expansion of circulating Vγ9 / Vδ1 T cells in a patient with a syndrome of recurrent fever: evidence for an unusual antigen-driven process leading to selection of recurrent motifs within TCR junctional loops of diverse lengths

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