Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review focuses on the response to foreign major histocompatibility complex (MHC) molecules by T lymphocytes. This phenomenon is characterized by a uniquely strong primary immune reaction, due to a very high precursor frequency of alloreactive T cells. This is manifest in vitro in the mixed lymphocyte reaction (MLR) and in vivo leads to allograft rejection and to graft versus host disease. Understanding this phenomenon requires an understanding of the nature of the ligand recognized by alloreactive T cells. In this review we report evidence in support of the two hypotheses which have been put forward to account for the high precursor frequency of anti-MHC alloreactive T cells. The high determinant hypothesis emphasized the implication of direct contact between the T cell receptor and the MHC molecule; the multiple binary complex hypothesis envisages that alloreactive T cells are specific for self peptide bound by the foreign MHC molecule. With these two lines of apparently contradictory evidence in mind we propose two distinct models to account for the phenomenon of allorecognition and to accommodate it within a self-MHC-restricted T cell repertoire. Which model is most applicable to a particular alloresponse is largely determined by the structural relationship between the responder and the stimulator MHC molecules.
 ...
PMID:The molecular basis of allorecognition of major histocompatibility complex molecules by T lymphocytes. 195 30

It is necessary that the two signals are required in T cells activation. The first signal is specific, which T cell receptor could recognize and bind MHC molecule by antigen-presenting cells. Another one is nonspecific, which results from CD28/B7/CTLA4 molecules on T cells and antigen-presenting cells. The both of signals regulate function of T cells such as the activation, proliferation and secreting cytokines. CTLA4 showed the up-regulation in CD28/B7 costimulatory pathway as a negative signal. The immunosuppression could occur by blocking CD28/B7 pathway. It provided useful method for immunotherapy in the autoimmune diseases and graft-versus-host disease. But then, the activation of CD28/B7 could be valuable for the immune system recognizing and eliminating tumor cells.
 ...
PMID:[CD28/B7 costimulating signal and its clinical significance]. 1251 1

Minor histocompatibility antigens (mHags) are polymorphic peptides presented to T lymphocytes restricted by the MHC molecule. It has been reported that disparities of mHags are a potential risk factor for GVHD after hematopoietic SCT (HSCT). Here we observed allelic frequencies of HA-1, -2 and -8 in 139 Korean healthy individuals using PCR-sequence-specific primers, and analyzed the correlation between disparity of these mHags and acute GVHD (aGVHD) in 54 patients who underwent HSCT from unrelated HLA-identical donors. The allelic frequencies in Korean healthy individuals were 39.6 and 60.4% for HA-1(H) and HA-1(R), 92.4 and 7.6% for HA-2(M) and HA-2(V), 36.7 and 63.3% for HA-8(R) and HA-8(P), respectively. The frequencies of mHags incompatibility known to be associated with aGVHD were 16.7% in HA-1, 0% in HA-2 and 25.9% in HA-8. However, the statistically significant association of aGVHD with these mHags incompatibility was not found between healthy donors and leukemia patients after unrelated HSCT. This first report about mHags in Koreans may be helpful in further defining the clinical impact of mHags disparities in HSCT and in comparing with other populations.
 ...
PMID:Distribution of the minor histocompatibility antigens in Korean population and disparities in unrelated hematopoietic SCT. 1770 Jun 1

The study of human T lymphocyte biology often involves examination of responses to activating ligands. T cells recognize and respond to processed peptide antigens presented by MHC (human ortholog HLA) molecules through the T cell receptor (TCR) in a highly sensitive and specific manner. While the primary function of T cells is to mediate protective immune responses to foreign antigens presented by self-MHC, T cells respond robustly to antigenic differences in allogeneic tissues. T cell responses to alloantigens can be described as either direct or indirect alloreactivity. In alloreactivity, the T cell responds through highly specific recognition of both the presented peptide and the MHC molecule. The robust oligoclonal response of T cells to allogeneic stimulation reflects the large number of potentially stimulatory alloantigens present in allogeneic tissues. While the breadth of alloreactive T cell responses is an important factor in initiating and mediating the pathology associated with biologically-relevant alloreactive responses such as graft versus host disease and allograft rejection, it can preclude analysis of T cell responses to allogeneic ligands. To this end, this protocol describes a method for generating alloreactive T cells from naive human peripheral blood leukocytes (PBL) that respond to known peptide-MHC (pMHC) alloantigens. The protocol applies pMHC multimer labeling, magnetic bead enrichment and flow cytometry to single cell in vitro culture methods for the generation of alloantigen-specific T cell clones. This enables studies of the biochemistry and function of T cells responding to allogeneic stimulation.
...
PMID:Generation of human alloantigen-specific T cells from peripheral blood. 2549 Feb 83