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Millions of RBC units are transfused throughout the world annually. Even though each RBC unit contains multiple foreign donor antigens, only a minority of transfusion recipients will develop detectable RBC alloantibodies. Some factors that influence humoral immune responsiveness to transfused RBCs are obvious, including the necessity of being exposed to a foreign antigen that the immune system can process and present. Mathematically, however, every RBC transfusion meets those criteria. Thus, it remains unclear why some patients form alloantibodies (‘responders’), while others may be transfused hundreds of times without becoming alloimmunised (‘non‐responders’). Studies in humans have found an association with CD4+ T‐cell markers and responsiveness to transfused RBCs, and have also identified acute or chronic inflammatory disease states as risk factors for alloantibody development. Studies in animal models, which allow single variables to be isolated, have led to an understanding of the critical role played by dendritic cells in transfusion‐associated RBC alloimmunisation. Murine studies have further established that non‐responsiveness to transfused RBCs equates to antigen‐specific tolerance in some settings: alloantibodies develop to RBCs expressing some blood group antigens only when the initial RBC exposure occurs in close association with a danger signal. Additional studies are needed in humans and in animal models to further understand the complex variables that determine when and how a humoral immune response may be initiated against transfused RBC antigens, such that strategies for preventing alloimmunisation and its harmful effects in transfusion and pregnancy scenarios can be developed. [ABSTRACT FROM AUTHOR]

Studies of major histocompatibility complex (MHC) diversity in non-model vertebrates typically focus on structure and sequence variation in the antigen-presenting loci: the highly variable and polymorphic class I and class IIB genes. Although these studies provide estimates of the number of genes and alleles/locus, they often overlook variation in functionally related and co-inherited genes important in the immune response. This study utilizes the sequence of the MHC B-locus derived from a commercial turkey to investigate MHC variation in wild birds. Sequences were obtained for nine interspersed MHC amplicons (non-class I/II) from each of 40 birds representing 3 subspecies of wild turkey (Meleagris gallopavo). Analysis of aligned sequences identified 238 single-nucleotide variants approximately one-third of which had minor allele frequencies >0.2 in the sampled birds. PHASE analysis identified 70 prospective MHC haplotypes in the wild turkeys, whereas a combined analysis with commercial birds identified almost 100 haplotypes in the species. Denaturing gradient gel electrophoresis (DGGE) of the class IIB loci was used to test the efficacy of single-nucleotide polymorphism (SNP) haplotyping to capture locus-wide variation. Diversity in SNP haplotypes and haplotype sharing among individuals was directly reflected in the DGGE patterns. Utilization of a reference haplotype to sequence interspersed regions of the MHC has significant advantages over other methods of surveying diversity while identifying high-frequency SNPs for genotyping. SNP haplotyping provides a means to identify both divergent haplotypes and homozygous individuals for assessment of immunological variation in wild and domestic populations. [ABSTRACT FROM AUTHOR]

Background and Objectives Transfusion of allogeneic platelet products can result in antibodies against donor major histocompatibility complex (MHC) I antigens, leading to a refractory state to subsequent platelet transfusions. However, there is disagreement in the field regarding the molecular mechanisms of humoral alloimmunization. One hypothesis states that donor MHC II is a requirement for alloimmunization. However, other studies have suggested that donor MHC I is alone sufficient and MHC II is not required. Materials and Methods We utilized a mouse model of anti-MHC I alloimmunization to transfused blood, which employed donors with a complete deletion of all MHC II genes. BALB/c (H-2d) recipients were transfused with blood from either C57BL/6 (H-2b) or MHC II null donors on a C57BL/6 background. Anti-MHC I alloimmunization was monitored by indirect immunofluorescence. Results Recipients of either wild type or MHC II null blood produced equivalent humoral responses against donor MHC I antigens. However, there was variation in the relative amounts of IgG subclasses. Conclusion These data reject the hypothesis that donor MHC II expression is required for alloimmunization to MHC I antigens. [ABSTRACT FROM AUTHOR]