What Is Direct Allorecognition?

Boardman, Dominic A.; Jacob, Jacinta; Smyth, Lesley A.; Lombardi, Giovanna; Lechler, Robert I.

doi:10.1007/s40472-016-0115-8

Cited by 28 publications

(24 citation statements)

References 92 publications

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“…This arteriovenous dilatation may lead to engorgement and stagnation of blood and decrease in its flow, resulting in hypoxia and ischemia of the salivary gland tissues. Sirolimus has antiangiogenic activities linked to decrease in production of vascular endothelial growth factor and markedly inhibited response of vascular endothelial cells to stimulate VEGF (11) . Ultra structurally the mitochondria of the acinar and ductal cells appeared pleomorphic and vacuolated with total or subtotal loss of cristea and their possible rupture.…”

Section: Discussionmentioning

confidence: 99%

The Effect of the Immunosuppressive Drug Sirolimus on structure of the Submandibular Salivary Glands of the Rat

Soliman

Ghali

Taha

2019

Suez Canal University Medical Journal

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Background: Submandibular salivary glands are responsible for secretion of major amount of saliva which is important for normal oral environment of the oral cavity. Aim: to evaluate the effect of the Immunosuppressive drug Sirolimus on structure and immunohistochemistry of the submandibular salivary glands of the rats. Material and Methods Forty healthy adult male albino rats (body weight 150 -180 gram) were divided into two equal groups 20 animals each. Group 1 served as controls while group 2 were treated with the immunosuppressive drug sirolimus (rapamycin). Control group were subdivided into two subgroups subgroup 1.1: received ethanol and saline in comparable volume to group 2 and same route of administration while subgroup 1.2 were left untreated. After 3 months, rats were sacrificed and specimens of the right side of submandibular salivary glands were stained with H & E and Immunoperoxidase. While specimens of the left side were examined with transmission electron microscope. Results: Histologically, by H & E, both control subgroups showed normal structure of submandibular salivary gland. While, rats administrated sirolimus showed altered structure. Using TEM, the ultrastructural of submandibular salivary glands of both control subgroups showed normal architecture. While, sirolimus treatedgroup revealed degeneration in the glands acinar and ductal cells. Immunohistochemical findings showed normal staining reactivity of submandibular salivary gland of the control group while, sirolimus-treated group showed marked reduction in their staining reaction. Conclusion: Sirolimus administration cause structural and ultrastructural alterations in the parenchymal and stromal elements of the submandibular salivary gland that affect the salivary secretion and may lead to detrimental effect on oral health.

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Section: Discussionmentioning

confidence: 99%

The Effect of the Immunosuppressive Drug Sirolimus on structure of the Submandibular Salivary Glands of the Rat

Soliman

Ghali

Taha

2019

Suez Canal University Medical Journal

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“…The drivers of TCR alloreactivity have been variously attributed to a TCR focus on unique allopeptides presented by allo-MHC (peptide-centric) or to a TCR misfocus on polymorphic amino acids on the α-helices of allo-MHC peptide-binding grooves (MHC-centric) (37)(38)(39). The surprising specificity of many alloreactive TCRs and structural studies of alloreactive complexes have challenged these theories (3,12,13).…”

Section: Discussionmentioning

confidence: 99%

How an alloreactive T-cell receptor achieves peptide and MHC specificity

Wang

Singh

Spear

et al. 2017

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

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T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2 − individual received an HLA-A2 + liver allograft. HCV1406 was subsequently shown to recognize the HCV nonstructural protein 3 (NS3):1406-1415 epitope with high specificity when presented by HLA-A2. We show that NS3/HLA-A2 recognition by the HCV1406 TCR is critically dependent on features unique to both the allo-MHC and the NS3 epitope. We also find cooperativity between structural mimicry and a crucial peptide "hot spot" and demonstrate its role, along with the MHC, in directing the specificity of allorecognition. Our results help explain the paradox of specificity in alloreactive TCRs and have implications for their use in immunotherapy and related efforts to manipulate TCR recognition, as well as alloreactivity in general.T-cell receptor | peptide-MHC | structure | alloreactivity | specificity

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“…Rejection can be T‐cell‐mediated (CMR), antibody‐mediated (AbMR) or both (Sellarés et al, ; Venner et al, ). CMR occurs as the result of direct interaction between the T‐cell receptor and the foreign HLA–peptide combination leading to activation of the T cell (Boardman, Jacob, Smyth, Lombardi, & Lechler, ). AbMR requires an inflammatory response and T h cell costimulation producing antibody which recognizes foreign HLA molecules (Batista & Harwood, ; Mitchison, ).…”

Section: Introductionmentioning

confidence: 99%

Factors affecting HLA expression: A review

Carey

Poulton

Poles

2019

Int J Immunogenetics

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The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)‐specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross‐match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA‐specific antibody is the only variable in the assessment of transplant risk, this is not the case. Transplant immunologists recognize that some HLA antigens are expressed at levels a magnitude lower than others (e.g., HLA‐C, HLA‐DQ), but within loci, and between different cell types there are many factors that influence HLA expression in both resting and activated cells. HLA is not usually expressed without the specific promoter proteins NLRC5, for HLA class I, and CIITA, for class II. The quantity of HLA protein production is then affected by factors including promoter region polymorphisms, alternative exon splice sites, methylation and microRNA‐directed degradation. Different loci are influenced by multiple combinations of these control mechanisms making prediction of HLA regulation difficult, but an ability to measure the cellular expression of each HLA antigen, in conjunction with knowledge of circulating HLA‐specific antibody, would lead to a more informed algorithm to assess transplant risk.

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What Is Direct Allorecognition?

Cited by 28 publications

References 92 publications

The Effect of the Immunosuppressive Drug Sirolimus on structure of the Submandibular Salivary Glands of the Rat

The Effect of the Immunosuppressive Drug Sirolimus on structure of the Submandibular Salivary Glands of the Rat

How an alloreactive T-cell receptor achieves peptide and MHC specificity

Factors affecting HLA expression: A review

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