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The Role of HLA-C in Allogeneic Hematopoietic Cell Transplantation

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HLA-C was recognized as a classical transplantation determinant long after HLA-A and HLA-B. Its low level of expression and lack of robust serologic typing reagents impeded investigation of this locus. In the DNA era, the availability of PCR-based methods has afforded investigators the tools with which to ...

HLA-C was recognized as a classical transplantation determinant long after HLA-A and HLA-B. Its low level of expression and lack of robust serologic typing reagents impeded investigation of this locus. In the DNA era, the availability of PCR-based methods has afforded investigators the tools with which to study HLA-C diversity and the implications of this variation on alloreactivity in blood, marrow and cord blood transplantation. Available evidence demonstrates that HLA-C is a polymorphic locus, shows strong positive linkage disequilibrium with HLA-B on extended HLA haplotypes. Matching between the patient and the stem cell source is associated with lower overall risks of graft-versus-host disease (GVHD). The likelihood of identifying suitable stem cell sources for patients who lack HLA-matched donors, however, remains a challenge, and emphasizes the need to define mismatches that do not increase post-transplant risks. Information on the role of HLA-C ligands in NK cell-mediated alloreactivity is a promising new area of research with implications for clinical translation to facilitate lower risks of post-transplant relapse.

In this Frontiers Research Topic, the functional consequences of HLA-C diversity, its role in T and NK-mediated alloreactions that impact risks of acute and chronic GVHD and relapse after blood, marrow and cord blood transplantation, will be highlighted.


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