Rearranged β t cell receptor genes in a helper t cell clone specific for lysozyme: No correlation between Vβ and MHC restriction

Goverman, Joan; Minard, Karyl I.; Shastri, Nilabh; Hunkapiller, Tim; Hansburg, Daniel; Sercarz, Eli E.; Hood, Leroy

doi:10.1016/0092-8674(85)90345-9

Cited by 118 publications

(43 citation statements)

References 37 publications

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“…Recently, it has been shown that two helper T-cell clones with different antigen and class II restriction specificities use the same V113 gene segment (41). In another study, it was shown that the same V13 gene is used in a class I-restricted CTL clone and in a class II-restricted helper T-cell clone (42).…”

Section: Discussionmentioning

confidence: 99%

T-cell receptor variable region gene usage in T-cell populations.

Garman¹,

Ko²,

Vulpe³

et al. 1986

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

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We have examined T-cell receptor alpha- and beta-chain variable (V) region gene usage in T-cell populations predicted to have different major histocompatibility complex-restriction specificities. Using a sensitive ribonuclease protection assay to measure T-cell receptor mRNA levels, we found no striking differences in the usage of three V alpha genes and three V beta genes in T-cell populations from three congeneic H-2-disparate strains of mice and between the mutually exclusive Ly2+ L3T4- and Ly2- L3T4+ T-cell subpopulations. These results suggest that major histocompatibility complex restriction cannot be explained by the differential usage of nonoverlapping V alpha or V beta gene pools. In contrast, striking but unpredictable differences were seen in V gene usage in populations of T cells selected by activation with particular alloantigens.

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Section: Discussionmentioning

confidence: 99%

T-cell receptor variable region gene usage in T-cell populations.

Garman¹,

Ko²,

Vulpe³

et al. 1986

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

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“…DNA prepared from 25 clones was digested with Hind III, Eco RI, and Bam HI, and Southern blots were tested for TCR rearrangements, using a series of oz and (3 TCR probes . 5 of the 25 clones (11,19,14,23, and 28) turned out to be repeated isolates, since they were identical in terms of strain of origin, immunization number, and all primary and secondary TCR rearrangements with another clone (Tables II and III). However, the remaining 20 clones could be unequivocally judged as unique by the same criteria .…”

Section: Resultsmentioning

confidence: 99%

Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

Falcioni¹,

Dembić²,

Müller³

et al. 1990

The Journal of Experimental Medicine

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Bovine insulin(BI)-specific I-Ab-restricted T cell clones have been characterized for fine specificity and TCR gene usage. We have demonstrated that mouse strains carrying H-2b on three different genetic backgrounds (C57BL, BALB, and 129) rearrange and express the V beta 6 gene in a large proportion (36%) of insulin-specific clones. In these strains, the non-MHC background did not seem to influence TCR gene usage in response to BI. The V beta 6+ clones appeared to be selected by the antigen. In contrast, no V beta 6+ clones could be isolated from (B6 x DBA/2)F1 mice, where V beta 6+ (and V beta 8.1+) T cells are deleted by self tolerance to Mls-1a. Thus, although a small proportion of residual V beta 6+ cells had been demonstrated in Mls-1a mice, these cells could not be retrieved in a response that uses V beta 6 predominantly. In functional terms, therefore, the deletion of V beta 6 by self tolerance appears to be complete. Instead of V beta 6, the majority (up to 60%) of I-Ab- as well as I-Ad-restricted insulin-specific clones from the (B6 x DBA/2)F1 mice expressed V beta 8.2 and V beta 8.3. This shift of gene usage was not accompanied by any detectable change in the fine specificity pattern of response. Thus, in the insulin-specific response, the flexibility of T cell repertoire fully compensates for deletions caused by self tolerance.

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“…Alternatively, two rearranged bands observed after either restriction enzyme digestion could represent a productive and a nonproductive rearrangement in a single clone (31,32). It is unlikely that two productive rearrangements took place in a single clone, since there is evidence that at the protein level only one allele is expressed in any given cell (33)(34)(35). Similarly, it is unlikely that all of the observed bands represent only nonproductive D-J rearrangements, since common nonproductive rearrangements detectable by Southern blot analysis are not reported in heterogeneous T-cell populations and have not been observed in our control studies.…”

Section: Discussionmentioning

confidence: 99%

Clonal dominance among T-lymphocyte infiltrates in arthritis.

Stamenkovic

Stegagno

Wright

et al. 1988

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

239

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Synovial membranes in patients with rheumatoid arthritis as well as other types of chronic destructive inflammatory arthritis contain infiltrates of activated T lymphocytes that probably contribute to the pathogenesis of the disease. In an effort to elucidate the nature of these infiltrates, interleukin 2 (IL-2)-responsive T lymphocytes were grown out of synovial fragments from 14 patients undergoing surgery for advanced destructive inflammatory joint disease. Eleven of the samples examined were from patients with classical rheumatoid arthritis, while three others were obtained from individuals with clinical osteoarthritis. Southern blot analysis of T-cell receptor (TCR) 13-chain genes in 13 of 14 cultures showed distinct rearrangements, indicating that each culture was characterized by the predominance of a limited number of clones. T-cell populations from peripheral blood stimulated with a variety of activators and expanded with IL-2 did not demonstrate evidence of similar clonality in long-term culture.These results suggest that a limited number of activated T-cell clones predominate at the site of tissue injury in rheumatoid synovial membranes as well as in other types of destructive inflammatory joint disease. Further characterization of these T-cell clones may aid our understanding of the pathogenesis of these rheumatic disorders.

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Rearranged β t cell receptor genes in a helper t cell clone specific for lysozyme: No correlation between Vβ and MHC restriction

Cited by 118 publications

References 37 publications

T-cell receptor variable region gene usage in T-cell populations.

T-cell receptor variable region gene usage in T-cell populations.

Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

Clonal dominance among T-lymphocyte infiltrates in arthritis.

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