Click on the article title to read more.

Summary: One of the major factors that have contributed to improving the outcomes of Stem Cell Transplantation is progress made in the field of human leucocyte antigen(s) (HLA). This is evident not only in developing techniques for rapid and accurate tissue typing, but also in the greatly improved understanding of the HLA system and the impact of HLA matching on transplant complications. It is now accepted that high‐resolution HLA matching for transplant recipients and unrelated donors is associated with the best clinical outcomes. The most important HLA determinants are the six ‘classical’ polymorphic HLA loci: HLA‐A, ‐B, ‐C, ‐DRB1,‐DQB1, ‐DPB1. For several years, based on the outcome of numerous studies, a 10/10 matched donor (HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1) was considered the ideal. The impact of HLA‐DPB1 has been less clear, in view of reduced likelihood of patient/donor matching for this locus. More recently, several large studies have questioned the importance of HLA‐DQB1 matching on outcome. Based on the findings of recent studies, the current gold standard unrelated donor is believed to be one matched for 8/8 alleles at high resolution i.e. matched for HLA‐A, ‐B, ‐C, ‐DRB1, however, in certain circumstances, mismatches may be tolerated and/or permissive.

Polymorphisms located within the MHC have been linked to many disease outcomes by mechanisms not yet fully understood in most cases. Variants located within untranslated regions of HLA genes are involved in allele-specific expression and may therefore underlie some of these disease associations. We determined sequences extending nearly 2 kb upstream of the transcription start site for 68 alleles from 57 major lineages of classical HLA class I genes. The nucleotide diversity within this promoter segment roughly follows that seen within the coding regions, with HLA-B showing the highest (∼1.9%), followed by HLA-A (∼1.8%), and HLA-C showing the lowest diversity (∼0.9%). Despite its greater diversity, HLA-B mRNA expression levels determined in 178 European Americans do not vary in an allele- or lineage-specific manner, unlike the differential expression levels of HLA-A or HLA-C reported previously. Close proximity of promoter sequences in phylogenetic trees is roughly reflected by similarity of expression pattern for most HLA-A and -C loci. Although promoter sequence divergence might impact promoter activity, we observed no clear link between the phylogenetic structures as represented by pairwise nucleotide differences in the promoter regions with estimated differences in mRNA expression levels for the classical class I loci. Further, no pair of class I loci showed coordinated expression levels, suggesting that distinct mechanisms across loci determine their expression level under nonstimulated conditions. These data serve as a foundation for more in-depth analysis of the functional consequences of promoter region variation within the classical HLA class I loci.

Human cytomegalovirus (hCMV) infection is usually asymptomatic but may cause disease in immunocompromised hosts. It has been reported that hCMV infection may shape the NK cell receptor (NKR) repertoire in adult individuals, promoting a variable expansion of the CD94/NKG2C⁺ NK cell subset. We explored the possible relationship between this viral infection and the expression pattern of different NKR including CD94/NKG2C, CD94/NKG2A, immunoglobulin‐like transcript 2 (ILT2, CD85j), KIR2DL1/2DS1, KIR3DL1, and CD161 in peripheral blood lymphocytes from healthy children, seropositive (n=21) and seronegative (n=20) for hCMV. Consistent with previous observations in adults, a positive serology for hCMV was associated with increased numbers of NKG2C⁺ NK and T cells as well as with ILT2⁺ T lymphocytes. Moreover, the proportions of CD161⁺ and NKG2C⁺CD56⁻CD3⁻ NK cells also tended to be increased in hCMV⁺ individuals. Excretion of the virus was associated with higher proportions of NKG2C⁺ NK cells. Altogether, these data reveal that hCMV may have a profound influence on the NKR repertoire in early childhood.