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The Human Leukocyte Antigen (HLA) system, encoded on the short (p) and long (q) arms of chromosome 6, plays a pivotal role in the regulation of immune responses and the success of organ transplantation. As of 2024, the HLA gene database has cataloged 38,004 alleles, reflecting the system’s extraordinary polymorphism and its centrality in determining graft compatibility, rejection, and tolerance. This chapter explores the structural organization, biochemical composition, and functional specialization of HLA Class I, II, and III molecules, detailing their roles in antigen presentation and immune surveillance. Special emphasis is placed on the molecular architecture of these glycoproteins, their peptide-binding motifs, and the signaling pathways they influence. Furthermore, we present a case study involving a patient who experienced ischemia-reperfusion injury following transplantation. Through tailored immunomodulatory and supportive interventions, graft function was successfully restored, illustrating the translational bridge between molecular immunogenetics and clinical outcomes. The case underscores the relevance of HLA typing, donor-recipient matching, and post-transplant monitoring in optimizing graft survival. This integrative perspective enhances our understanding of how the HLA system’s molecular complexity informs clinical decision-making in transplant medicine.

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HLA Structure, Function, and Clinical Implications in Transplantation: A Case-Based and Molecular Perspective

  • 章节

  • 发表日期：

    2025年

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  • Sathya Selvarajan,
  • Jyothipriya Jyothindrakumar,
  • Milly Mathew,
  • Georgi Abraham

摘要

The Human Leukocyte Antigen (HLA) system, encoded on the short (p) and long (q) arms of chromosome 6, plays a pivotal role in the regulation of immune responses and the success of organ transplantation. As of 2024, the HLA gene database has cataloged 38,004 alleles, reflecting the system’s extraordinary polymorphism and its centrality in determining graft compatibility, rejection, and tolerance. This chapter explores the structural organization, biochemical composition, and functional specialization of HLA Class I, II, and III molecules, detailing their roles in antigen presentation and immune surveillance. Special emphasis is placed on the molecular architecture of these glycoproteins, their peptide-binding motifs, and the signaling pathways they influence. Furthermore, we present a case study involving a patient who experienced ischemia-reperfusion injury following transplantation. Through tailored immunomodulatory and supportive interventions, graft function was successfully restored, illustrating the translational bridge between molecular immunogenetics and clinical outcomes. The case underscores the relevance of HLA typing, donor-recipient matching, and post-transplant monitoring in optimizing graft survival. This integrative perspective enhances our understanding of how the HLA system’s molecular complexity informs clinical decision-making in transplant medicine.