The molecular basis of alloreactivity

Lechler, Robert I.; Lombardi, Giovanna; Batchelor, J. R.; Reinsmoen, Nancy L.; Bach, Fritz H.

doi:10.1016/0167-5699(90)90033-6

Cited by 261 publications

(105 citation statements)

References 34 publications

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“…Molecular mimicry will explain the considerable extent of the allogeneic immune response. There is a large number of different class I or II MHC/peptide epitopes of the donor that may be recognized by different T cell clones of the recipient by molecular mimicry (29,52). However, stimulation of T cells of the recipient by donor APCs that may lack costimulatory molecules will lead to anergy, reducing the significance of this response after the early post-transplantation period (60 -64).…”

Section: Discussionmentioning

confidence: 99%

“…MHC molecules of the donor may directly present peptides to the T cells of the recipient (31). It has been proposed that molecular mimicry is the basis of this recognition (29,52). Molecular mimicry will explain the considerable extent of the allogeneic immune response.…”

Section: Discussionmentioning

confidence: 99%

“…However, stimulation of T cells of the recipient by donor APCs that may lack costimulatory molecules will lead to anergy, reducing the significance of this response after the early post-transplantation period (60 -64). The indirect recognition pathway involves presentation by APC of the recipient to T cells of the recipient of epitopes comprised of MHC molecules of the recipient and antigenic peptides derived from MHC Ags of the donor (27)(28)(29)(30)(31)(32)(33)(34)(35). The later should be available in high quantities in the graft, because of cell destruction at the site of the graft and possible shedding of MHC molecules.…”

Section: Discussionmentioning

confidence: 99%

“…DeBruyne et al (59) reported restricted V␤-gene segment use by bronchoalveolar lavage-derived T cell lines from patients with human lung allografts before and during rejection episodes. Two different mechanisms of Ag presentation, the direct and the indirect, are responsible for the recognition of organ drafts by T cells of the recipient (27)(28)(29)(30)(31)(32)(33)(34)(35). The direct recognition pathway involves recognition of allogeneic MHC/peptide complexes expressed on dendritic cells (passenger leukocytes) of the donor by T cells of the recipient.…”

Section: Discussionmentioning

confidence: 99%

“…Both are members of the Ig supergene family (26). T cells of the recipient recognize organ grafts by two different pathways of Ag presentation, the direct and the indirect (27)(28)(29)(30)(31)(32)(33)(34)(35). Antigenic specificity for the TCR is primarily associated with the sequences of the hypervariable, or CDR3, part of the ␤-chain TCR transcript (36 -39).…”

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confidence: 99%

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Coronary Arteries from Human Cardiac Allografts with Chronic Rejection Contain Oligoclonal T Cells: Persistence of Identical Clonally Expanded TCR Transcripts from the Early Post-Transplantation Period (Endomyocardial Biopsies) to Chronic Rejection (Coronary Arteries)

Slachta

Jeevanandam²,

Goldman

et al. 2000

The Journal of Immunology

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Chronic cardiac allograft rejection presents pathologically as graft arteriosclerosis (GA) characterized by recipient T cell and monocyte infiltration. To determine whether oligoclonal T cells are present in coronary arteries of cardiac allografts from patients with GA, we conducted sequencing analysis of β-chain TCR transcripts from these explanted coronary arteries using the nonpalindromic adaptor-PCR. Substantial proportions of identical β-chain TCR transcripts in three of five patients were observed, clearly demonstrating the presence of oligoclonal T cells. TCR transcripts from the arteries of two other patients were relative heterogeneous. High proportions of identical CDR3 β-chain TCR motifs were found in each patient. GENEBANK/EMBL/SWISS PROT database comparison of all sequences revealed that these β-chain TCR transcripts were novel. Using Vβ-specific PCR (independent amplification), we found in patient GA03 that the TCR transcript that was clonally expanded in the left anterior descending artery after nonpalindromic adaptor-PCR was also clonally expanded in the right coronary artery of the same allograft. These results demonstrate that this TCR transcript was clonally expanded at different anatomic sides of the cardiac allograft in a systemic manner. In two patients identical β-chain TCR transcripts that were found to be clonally expanded in the coronary arteries of their explanted cardiac allografts were also found to be clonally explanted in endomyocardial biopsies collected 17 and 21 mo earlier from each patient. The presence of oligoclonal populations of T cells in the rejected graft suggest that these T cells have undergone specific Ag-driven proliferation and clonal expansion early on within the graft and persist throughout the post-transplantation period.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Coronary Arteries from Human Cardiac Allografts with Chronic Rejection Contain Oligoclonal T Cells: Persistence of Identical Clonally Expanded TCR Transcripts from the Early Post-Transplantation Period (Endomyocardial Biopsies) to Chronic Rejection (Coronary Arteries)

Slachta

Jeevanandam²,

Goldman

et al. 2000

The Journal of Immunology

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Antigen presentation by keratinocytes induces tolerance in human T cells

Bal¹,

McIndoe²,

Denton³

et al. 1990

Eur J Immunol

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166

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Antigen recognition by interleukin 2 (IL 2)-producing T lymphocytes can lead to two distinct outcomes, depending on the nature of the antigen-presenting cell. Recognition of antigen presented by specialized antigen-presenting cells leads to T cell activation; in contrast, antigen presentation by cells which lack "accessory function" can lead to a state of specific nonresponsiveness, which is characterized by a failure to produce IL 2. We have shown in this study that co-culture of an HLA-DR1/4-restricted, influenza hemagglutinin-specific T cell clone with a specific peptide presented by interferon-gamma-induced DR4-expressing keratinocytes causes tolerance induction. This effect was DR restricted, in that it required pre-incubation of the T cell clone with keratinocytes expressing an appropriate DR type (DR4Dw14). The induction of T cell tolerance was also antigen specific; no inhibition resulted from pre-incubation of the clone with an irrelevant peptide. Furthermore cell to cell contact appeared to be necessary, and the addition of supernatant from interferon-gamma-induced keratinocytes did not cause any inhibition. This phenomenon may have relevance to the immunogenicity of transplanted cultured keratinocytes and to the effects of major histocompatibility complex class II induction on non-bone marrow-derived cells. Presentation of tissue-specific autoantigens by cells such as keratinocytes may provide a mechanism of avoiding, rather than stimulating, autoimmune reactions in the context of a local inflammatory response.

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Parasite‐accessory cell interactions in Theileriosis. Antigen presentation by Theileria annulata‐infected macrophages and production of continuously growing antigen‐presenting cell lines

Glass

Spooner

1990

Eur J Immunol

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Theileria annulata, a protozoan parasite of cattle, infects major histocompatibility complex (MHC) class II+ cells, particularly macrophages, and transforms them into continuously growing cell lines. We examined the effects of parasitism by T. annulata on antigen-presenting cell function. T. annulata-infected cells (TaH) presented ovalbumin (as measured by [3H]thymidine incorporation) to both resting autologous bovine T cells and ovalbumin-specific bovine CD4+ T cell lines. However, the former cells were also stimulated by TaH without exogenous antigen although to a lesser degree than in the presence of antigen. This "nonspecific" proliferation was not seen with the ovalbumin-specific T cell lines. The magnitude of response by resting T cells in the presence of antigen, to TaH or purified peripheral blood monocytes, was essentially similar. However, on a per cell basis fewer TaH were required. Considerably greater proliferation to antigen was seen with the ovalbumin-specific T cell lines in the presence of TaH compared to monocytes and again fewer TaH were required to elicit a response. The kinetics of processing did not appear to be substantially altered in TaH and the increased proliferation may be due to the elevated MHC class II expression of these cells. Genetic restriction studies with the T cell lines indicated that the restricting elements used to present ovalbumin by TaH were the same as those used by monocytes, as identified by an isoelectric focusing technique. The continuously growing cell lines provide us with a unique model for investigating parasite-accessory cell interactions in theileriosis. The augmented antigen presenting cell activity of TaH may play an important role in the pathogenesis of the disease. TaH will also provide us with a valuable resource for our antigen presentation studies. In particular, the enhanced antigen presentation by TaH enabled us to detect responses to lower levels of antigen, often an important consideration for experiments where the quantity of antigen available is the major limiting factor.

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The molecular basis of alloreactivity

Cited by 261 publications

References 34 publications

Coronary Arteries from Human Cardiac Allografts with Chronic Rejection Contain Oligoclonal T Cells: Persistence of Identical Clonally Expanded TCR Transcripts from the Early Post-Transplantation Period (Endomyocardial Biopsies) to Chronic Rejection (Coronary Arteries)

Coronary Arteries from Human Cardiac Allografts with Chronic Rejection Contain Oligoclonal T Cells: Persistence of Identical Clonally Expanded TCR Transcripts from the Early Post-Transplantation Period (Endomyocardial Biopsies) to Chronic Rejection (Coronary Arteries)

Antigen presentation by keratinocytes induces tolerance in human T cells

Parasite‐accessory cell interactions in Theileriosis. Antigen presentation by Theileria annulata‐infected macrophages and production of continuously growing antigen‐presenting cell lines

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