HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44 Natural Killer Cells in Ulcerative Colitis.

Background & Aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.

Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764).

A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44.

Natural killer (NK) cells can recognize virus-infected and stressed cells using activating and inhibitory receptors, many of which interact with HLA class I. Although early studies also suggested a functional impact of HLA class II on NK cell activity, the NK cell receptors that specifically recognize HLA class II molecules have never been identified. We investigated whether two major families of NK cell receptors, killer-cell immunoglobulin-like receptors (KIRs) and natural cytotoxicity receptors (NCRs), contained receptors that bound to HLA class II, and identified a direct interaction between the NK cell receptor NKp44 and a subset of HLA-DP molecules, including HLA-DP401, one of the most frequent class II allotypes in white populations.

The clinical impact of humoral immunity in pediatric renal transplantation.

The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months.

Beyond histology: lowering human leukocyte antigen antibody to improve renal allograft survival in acute rejection.

Background: The common endpoint in the treatment of antibody-mediated rejection (AMR) is functional reversal (creatinine levels). Reduction of human leukocyte antigen (HLA) antibody strength is not commonly considered as an essential endpoint for AMR resolution. The purpose of this study was to determine whether reduction in HLA antibody intensity in patients with histologic AMR reversal influences long-term renal allograft survival.

Epitopes of HLA-A, B, C, DR, DQ, DP and MICA antigens.

This chapter presents lists of HLA epitopes that have been defined to date. It also presents examples of reactions of mAb and eluted allosera with the class I, class II and MICAsingle antigen beads. To date, we have identified 110 class I epitopes, of which 47 were defined by mAbs and 63 by alloantibodies that were eluted from rHLA class I single antigen cell lines.

Detection of HLA and MICA antibodies before kidney graft failure.

390 serum samples taken from a series of 28 patients who lost their grafts were retrospectively investigated for antibodies by single antigen HLA Class I&II and MICA Luminex beads. In 20 patients with immunological failure, 10 patients had DSA, 16 had epitope-related NDSA, and 16 had NDSA or MICA antibodies. In 16 which increased antibodies leading up to the graft failure, DSA were found in 7 patients.

HLA class II DQ epitopes.

1. DQ epitopes were defined by studying the distinct reaction profiles of 17 allosera and 35 DQ-specific mouse monoclonal antibodies to HLA class II single antigen beads coated with purified recombinant DQ molecules. 2.