Real-time T-cell profiling identifies H60 as a major minor histocompatibility antigen in murine graft-versus-host disease

Choi, Eun Young; Christianson, Gregory J.; Yoshimura, Yoshitaka; Jung, Nadja; Sproule, Thomas J.; Malarkannan, Subramaniam; Joyce, Sebastian; Roopenian, Derry C.

doi:10.1182/blood-2002-05-1299

Cited by 72 publications

(81 citation statements)

References 40 publications

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“…Previous studies indicated that in the C57BL/6 anti-BALB.B response, H60-reactive CTL dominates over other minor H Ags (8,(15)(16)(17)35). However, at that time the magnitude of the H4 b response was difficult to ascertain accurately because the epitope was hitherto unknown.…”

Section: H4 B Is Immunodominantmentioning

confidence: 95%

“…For example, C57BL/6 CTL response to BALB.B minor H Ags is focused primarily on H2K b -restricted H60, but responses to H2K b -restricted H4 and H28 as well as to H2D b -restricted H7, H13, and HY alloantigens are also observed. The magnitude of the response to H60 is greater than those toward the other minor H Ags (15)(16)(17). This hierarchic T cell response, also observed in immunity to pathogens and tumors, is termed immune dominance (reviewed in Ref.…”

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confidence: 99%

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The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications

Yadav

Yoshimura

Boesteanu

et al. 2003

The Journal of Immunology

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Minor histocompatibility (H) Ag disparities result in graft-vs-host disease and chronic solid allograft rejection in MHC-identical donor-recipient combinations. Minor H Ags are self protein-derived peptides presented by MHC class I molecules. Most arise as a consequence of allelic variation in the bound peptide (p) that results in TCR recognizing the p/MHC as foreign. We used a combinational peptide screening approach to identify the immune dominant H2Kb-restricted epitope defining the mouse H4b minor H Ag. H4b is a consequence of a P3 threonine to isoleucine change in the MHC-bound peptide derived from epithelial membrane protein-3. This allelic variation also leads to phosphorylation of the H4b but not the H4a epitope. Further, ex vivo CD8+ T lymphocytes bind phosphorylated Ag tetramers with high efficiency. Although we document the above process in the minor H Ag system, posttranslational modifications made possible by subtle amino acid changes could also contribute to immunogenicity and immune dominance in tumor immunotherapeutic settings.

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Section: H4 B Is Immunodominantmentioning

confidence: 95%

mentioning

confidence: 99%

The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications

Yadav

Yoshimura

Boesteanu

et al. 2003

The Journal of Immunology

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“…2C); the complete 308-gene data set is shown in supplementary table I. 4 A partial list of the differentially expressed genes is provided in Table I to illustrate that the gene expression profile of anti-H7 a CD8 effector T cells was similar to that of effector CD8 T cells specific for viral or OVA epitopes (34 -36).…”

Section: Differential Gene Expression In H7 a Tet ϩ Vs Tet ϫ Cd8 T Cellsmentioning

confidence: 99%

“…S100a4 regulates cell cycle progression and differentiation, whereas Csf1r (Gene Expression Omnibus data sets 433 and 755), Ftl1 (43), and Edg8 (44) are up-regulated on activated relative to naive T cells, but definition of their precise roles awaits further studies. 4 The online version of this article contains supplemental material. a Ratios preceded by a minus sign (Ϫ) refer to transcripts that were down-regulated in H7 a Tet ϩ T cells, whereas remaining ratios relate to genes that were up-regulated in H7 a Tet ϩ T cells.…”

Section: Differential Gene Expression In Anti-h7 a Vs Anti-hy Cd8 Effmentioning

confidence: 99%

“…Strikingly, under the latter circumstances, CD8 T cells respond to only a few immunodominant epitopes and neglect other potentially immunogenic peptides (cryptic epitopes). Restriction of CD8 T cell responses to a few selected epitopes has been termed immunodominance, a central and robust feature of immune responses (1)(2)(3)(4)(5)(6)(7)(8). At face value, immunodominance is counterintuitive.…”

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Asynchronous Differentiation of CD8 T Cells That Recognize Dominant and Cryptic Antigens

Baron

Meunier

Caron

et al. 2006

The Journal of Immunology

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Restriction of T cell responses to a few epitopes (immunodominance) is a central feature of immune responses. We analyzed the entire transcriptome of effector CD8 T cells specific for a dominant (H7a) and a cryptic (HY) mouse Ag and performed a longitudinal analysis of selected T cell differentiation markers. We found that Ag specificity had a relatively modest influence on the repertoire of genes that are transcriptionally modulated by the CD8 T cell differentiation program. Although the differentiation programs of anti-H7a and anti-HY T cells were similar, they did not progress simultaneously. The expansion peak of anti-H7a T cells was reached on day 10 while that of anti-HY T cells was attained on days 15–20. Between days 10 and 20, anti-H7a T cells were in the contraction phase and anti-HY T cells in the expansion phase. Furthermore, expansion and development of effector function were well-synchronized in anti-H7a T cells but were disconnected in anti-HY T cells. We propose that, by leading to selective expansion of the fittest CD8 T cells, immunodominance may be beneficial to the host. Inhibition of the T cell response to cryptic Ag would ensure that host resources (APC, cytokines) for which T cells compete are devoted to T cells with the best effector potential. One implication is that favoring expansion of the fittest effector T cells in general may be more important than increasing the diversity of the T cell repertoire.

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Pathophysiology of acute graft‐versus‐host disease

Reddy

2003

Hematological Oncology

150

109

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Graft-versus-host disease (GVHD) has been the primary limitation to the wider application of allogeneic bone marrow transplantation (BMT). The pathophysiology of acute GVHD is complex and can be conceptualized to be a three-step process based on murine studies. In step 1, the conditioning regimen leads to the damage and activation of host tissues and induces the secretion of inflammatory cytokines. As a consequence, the expression of MHC antigens and adhesion molecules is increased enhancing the recognition of host alloantigens by donor T cells. Donor T-cell activation in step 2 is characterized by donor T cell interaction with host APCs and subsequent proliferation, differentiation and secretion of cytokines. Cytokines such as IL-2 and IFN-gamma enhance T-cell expansion, induce cytotoxic T cells (CTL) and natural killer (NK) cell responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. These inflammatory cytokines in turn stimulate production of inflammatory chemokines, thus recruiting effector cells into target organs. In step 3, effector functions of mononuclear phagocytes are triggered via a secondary signal provided by lipopolysaccharide (LPS) that leaks through the intestinal mucosa damaged during step 1. This mechanism may result in the amplification of local tissue injury and further promotion of an inflammatory response, which, together with the CTL and NK components, leads to target tissue destruction in the transplant host. The following review discusses the three-step process of the pathophysiology of experimental acute GVHD.

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Real-time T-cell profiling identifies H60 as a major minor histocompatibility antigen in murine graft-versus-host disease

Cited by 72 publications

References 40 publications

The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications

The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications

Asynchronous Differentiation of CD8 T Cells That Recognize Dominant and Cryptic Antigens

Pathophysiology of acute graft‐versus‐host disease

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