In vivo clonal dominance and limited T-cell receptor usage in human CD4+ T-cell recognition of house dust mite allergens.

Wedderburn, Lucy R.; O’Hehir, Robyn E; Hewitt, Colin R. A.; Lamb, Jonathan R.; Owen, Michael John

doi:10.1073/pnas.90.17.8214

Cited by 88 publications

(49 citation statements)

References 32 publications

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“…The two clones isolated from donor 008 have also persisted for 30 months to date. Previous reports have also documented long-term in vivo persistence of house dust mite-or heat shock protein-specific CD4+ T-cell clones in seronegative donors (26,27).…”

Section: Resultsmentioning

confidence: 96%

Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors.

Moss

Rowland‐Jones

Frodsham

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

153

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Section: Resultsmentioning

confidence: 96%

Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors.

Moss

Rowland‐Jones

Frodsham

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

153

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“…It is well established that restimulation of lines with Ag in vitro is similar to chronic stimulation in vivo, favoring the competitive outgrowth of clones of focused Ag specificity and TCR usage. Multiple clones carrying the same receptor have been viewed either as evidence of immunologically pertinent clonal expansion (48,49) or of the fortuitous, repeated isolation of sister clones (25). The fact that the "sister clones," which thrive and predominate, have different features when a single pool is separated into Th1 and Th2 culture wells suggests that these preferential expansions have a structural relevance in the Th1/Th1 context.…”

Section: Discussionmentioning

confidence: 99%

CD4 T Cells Selected by Antigen Under Th2 Polarizing Conditions Favor an Elongated TCRα Chain Complementarity-Determining Region 3

Boyton

Zaccai

Jones

et al. 2002

The Journal of Immunology

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The affinity of the MHC/peptide/TCR interaction is thought to be one factor determining the differentiation of CD4+ T cells into Th1 or Th2 phenotypes. To study whether CD4+ cells generated under conditions favoring Th1 or Th2 responses select structurally different TCRs, Th1 and Th2 clones and lines were generated from nonobese diabetic and nonobese diabetic H2-E transgenic mice against the peptides proteolipoprotein 56–70, glutamic acid decarboxylase65 524–543, and heat shock protein-60 peptides 168–186 and 248–264. Th1/Th2 polarization allowed the generation of clones and lines with fixed peptide specificity and class II restriction but differing in Th1/Th2 phenotype in which the impact on TCR selection and structure could be studied. The Th2 clones tended to use longer TCR complementarity-determining region (CDR)3α loops than their Th1 counterparts. This trend was confirmed by analyzing TCRα transcripts from Th1 and Th2 polarized, bulk populations. Molecular modeling of Th1- and Th2-derived TCRs demonstrated that Th2 CDR3α comprised larger side chain residues than Th1 TCRs. The elongated, bulky Th2 CDR3α loops may be accommodated at the expense of less optimal interactions between the MHC class II/peptide and other CDR loops of the TCR. We propose that CD4+ T cells selected from the available repertoire under Th2 polarizing conditions tend to have elongated TCR CDR3α loops predicted to alter TCR binding, reducing contact at other interfaces and potentially leading to impeded TCR triggering.

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“…In addition, CLA + CD8 + and CLA + CD4 + T cells derived from the peripheral blood of AD patients are equipotent in inducing IgE production by B cells and enhancing eosinophil survival (11). Dust mite-specific CD4 + T cell responses have been identified and the HLA class II-restricting elements defined for several Der P antigens (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The responses have been found in blood and lesional skin of affected individuals and following dust mite patch test challenge (21,26).…”

Section: Introductionmentioning

confidence: 96%

Allergen-specific CD8+ T cells and atopic disease

Seneviratne¹,

Jones²,

King³

et al. 2002

J. Clin. Invest.

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Considerable evidence suggests that IL-10 may have a role in the manifestation of atopic disease. We sought to test the hypothesis that at the single cell level, allergen-specific T cells have diminished IL-10 production capacity in severely affected atopics compared with asymptomatic atopics. We defined three A*0201-restricted Der p 1 CD8+ T cell epitopes. Using human leukocyte antigen-A*0201–peptide (HLA-A*0201–peptide) tetrameric complexes and enzyme-linked immunospot assays to analyze peripheral blood mononuclear cells from A*0201-positive severely symptomatic atopics, asymptomatic atopics, and nonatopic controls, we observed a significant association between the frequency of the Der p 1–specific CD8+ T cells and disease activity. The specific T cells expressed an antigen-experienced cell surface phenotype, and 45.7% were positive for cutaneous lymphocyte-associated antigen. The specific T cells were able to produce IFN-γ efficiently, but their IL-10 production was significantly reduced in severely affected atopics. In contrast, viral-specific CD8+ T cells were able to produce equivalent amounts of IL-10 in the severely affected atopics compared with asymptomatic atopics and nonatopics. Through defining the first human atopic allergen HLA class I epitopes, we have provided a possible cellular mechanism to link the previous association of low IL-10 levels and severe atopic disease. These data are consistent with a role for CD8+ T cells in atopic disease pathogenesis and may provide a basis for future T cell immunotherapy strategies

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In vivo clonal dominance and limited T-cell receptor usage in human CD4+ T-cell recognition of house dust mite allergens.

Cited by 88 publications

References 32 publications

Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors.

Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors.

CD4 T Cells Selected by Antigen Under Th2 Polarizing Conditions Favor an Elongated TCRα Chain Complementarity-Determining Region 3

Allergen-specific CD8+ T cells and atopic disease

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