Autoimmunity, microbial immunity and the immunological homunculus

Cohen, Irun R.; Young, Douglas B.

doi:10.1016/0167-5699(91)90093-9

Cited by 482 publications

(285 citation statements)

References 62 publications

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“…The responses were assessed by 3H-thymidine uptake. In healthy individuals (Figure l), 3H-thymidine uptake was significantly increased over background counts only when PBL from DR4+ and DR1+ individuals were stimulated with the M1 peptide (amino acid residues [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. This was detected in 5 of 7 such individuals (data from 3 subjects are shown).…”

Section: Resultsmentioning

confidence: 99%

“…It may not be necessary to block the MHC-binding site completely for peptide immunotherapy to be effective. MHC occupancy with an unrelated peptide may shift the balance of dominant and similarly MHC-restricted T cell clones within an organized and regulated lymphocyte network (16). Is it possible to block all MHC DR4-binding sites if this is required of IL-2 (13).…”

Section: Ra Dr4/1mentioning

confidence: 99%

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Lymphocyte responses to DR4/1‐restricted peptides in rheumatoid arthritis. The immunodominant T cell epitope on the 19‐kd mycobacterium tuberculosis protein

Tan

Farmiloe

Young

et al. 1992

Arthritis & Rheumatism

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Objective. Peptides presented by DR4/1 may be involved in the pathogenesis of rheumatoid arthritis (RA). T cell responses to DR4/1‐restricted peptides unrelated to the causative antigen may be altered in RA. Thus, DR4/1‐restricted lymphocyte responses in healthy volunteers and patients with RA were determined. Methods. Peripheral blood lymphocytes (PBL) and synovial lymphocytes were cultured with synthetic peptides spanning the 19‐kd Mycobacterium tuberculosis (MT) protein. Results. 3H‐thymidine uptake by PBL from 5 of 7 healthy individuals and 5 of 7 RA patients increased in response to the N‐terminal peptide (residues 1–20). Eleven fresh synovial fluid and 4 fresh synovial tissue (ST) lymphocyte samples did not proliferate in response to any of the peptides. However, the same T cell epitope was identified by ST lymphocytes when these were precultured. The N‐terminal peptide was not a common antibody‐binding site, unlike several of the other peptides. Conclusion. Similar responses by RA and normal PBL to a DR4/1‐restricted immunodominant T cell epitope on the 19‐kd MT protein were observed. The responses were more readily detected in PBL than in synovial lymphocytes. These observations may be relevant for assessing unrelated synthetic peptides in the development of DR4/1‐restricted peptide immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: Ra Dr4/1mentioning

confidence: 99%

Lymphocyte responses to DR4/1‐restricted peptides in rheumatoid arthritis. The immunodominant T cell epitope on the 19‐kd mycobacterium tuberculosis protein

Tan

Farmiloe

Young

et al. 1992

Arthritis & Rheumatism

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“…The term immunological homunculus [14,15,16] refers both to a set of empirical observations and to a set of theoretical conclusions derived from the following observations.…”

Section: The Immunological Homunculus Concept Of Autoimmunitymentioning

confidence: 99%

“…(i) These regulatory mechanisms function naturally to prevent autoimmune disease [14,16]. (ii) Autoimmune diseases arise from the failure of natural regulatory mechanisms to prevent or contain the autoimmune responses to injury or infection that arise naturally [14,16].…”

Section: Explanatory Hypothesesmentioning

confidence: 99%

“…(ii) Autoimmune diseases arise from the failure of natural regulatory mechanisms to prevent or contain the autoimmune responses to injury or infection that arise naturally [14,16]. (iii) The natural treatment of autoimmune disease is to activate the regulatory mechanisms, not to suppress the autoimmune clones: specific vaccination, not immunosuppression [21].…”

Section: Explanatory Hypothesesmentioning

confidence: 99%

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Peptide therapy for Type I diabetes: the immunological homunculus and the rationale for vaccination

2002

Diabetologia

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The autoimmune process that produces Type I (insulin-dependent) diabetes mellitus seems to respond favourably to therapeutic vaccination with a peptide of the 60 kDa heat shock protein. This article is a personal review of the observations and the thinking that gave rise to the idea of therapeutic peptide vaccination. The rationale for vaccination therapy is compared to other approaches aimed at specific immunological treatment for autoimmune disease. [Diabetologia (2002)

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Genetic control of natural antibody repertoires: I. IgH, MHC and TCRβ loci

Vasconcellos¹,

Nóbrega²,

Haury³

et al. 1998

Eur. J. Immunol.

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Global analysis of natural antibody repertoires has revealed a marked conservation of reactivity patterns within inbred mouse strains, and characteristic strain-specific differences. We have now analyzed the genetic control of reactivity repertoires, aiming at identifying the respective selection mechanisms. Multiparametric statistics of a large number of serum antibody reactivities scored by quantitative Western blot analyses using extracts from homologous tissues and bacteria readily distinguish the reactivity patterns of C57BL/6 and BALB/c, revealing homogeneity among genetically identical individuals. Antibody repertoires in the prototype strains can also be segregated from those expressed by the respective IgH congenics, BC.8 and CB.20, demonstrating that IgH-linked genes contribute to determining natural antibody repertoires. Conversely, strains sharing IgH haplotype also express distinct reactivity patterns, indicating that other genes participate in the selection of serum IgM repertoires. Two such non-IgH loci were now identified. Thus, analysis of four MHC-congenic strains demonstrated that MHC-linked control of natural antibody repertoires is likely to operate through differential selection of T cell repertoires, since (1) mice that are congenic at the TCR beta locus, and (2) BALB/c nude mice grafted at birth with pure thymic epithelium from either C57BL/6 or BALB/c also differ in their natural antibody repertoires.

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Autoimmunity, microbial immunity and the immunological homunculus

Cited by 482 publications

References 62 publications

Lymphocyte responses to DR4/1‐restricted peptides in rheumatoid arthritis. The immunodominant T cell epitope on the 19‐kd mycobacterium tuberculosis protein

Lymphocyte responses to DR4/1‐restricted peptides in rheumatoid arthritis. The immunodominant T cell epitope on the 19‐kd mycobacterium tuberculosis protein

Peptide therapy for Type I diabetes: the immunological homunculus and the rationale for vaccination

Genetic control of natural antibody repertoires: I. IgH, MHC and TCRβ loci

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