Immunology: Current Research
Open Access

Antigen presentation; Immune response; T cells; Adaptive immunity; Antigen-presenting cells; Immunological recognition; Human leukocyte antigen

Introduction

The immune system is a complex and highly coordinated network that defends the body against pathogens while maintaining tolerance to self-antigens. Central to this function is the ability of immune cells to recognize and respond to a vast array of foreign antigens. The Major Histocompatibility Complex (MHC) is a crucial component in this process, serving as a molecular platform for the presentation of peptide antigens to T lymphocytes [1]. Located on chromosome 6 in humans, the MHC is also referred to as the human leukocyte antigen (HLA) complex and exhibits an extraordinary degree of genetic polymorphism, which contributes to the diversity and adaptability of immune responses across individuals [2]. MHC molecules are divided into two primary classes—Class I and Class II—each with distinct roles in antigen processing and presentation. MHC Class I molecules present endogenous antigens, typically derived from intracellular pathogens such as viruses, to CD8⁺ cytotoxic T cells. In contrast, MHC Class II molecules present exogenous antigens, originating from extracellular pathogens, to CD4⁺ helper T cells [3]. This antigen presentation is a prerequisite for the activation and differentiation of T cells, which orchestrate subsequent immune responses, including antibody production, cytotoxic activity, and immune memory formation. Given its pivotal role in immune recognition, the MHC is not only vital in host defense but also has profound implications in clinical contexts such as organ transplantation, autoimmunity, vaccine development, and cancer immunotherapy [4]. This article explores the molecular mechanisms of MHC-mediated antigen presentation and its broader significance in shaping the immune landscape.

Discussion

The Major Histocompatibility Complex (MHC) is fundamental to the immune system’s ability to detect and respond to pathogens. By presenting peptide fragments on the cell surface, MHC molecules enable T cells to discriminate between self and non-self, triggering immune activation when foreign antigens are detected [5]. The highly polymorphic nature of MHC genes enhances this recognition by increasing the repertoire of peptides that can be presented, thus providing a population-level advantage against a wide range of pathogens. However, this polymorphism also poses challenges, particularly in transplantation medicine, where MHC mismatches between donor and recipient can lead to graft rejection [6],[7]. MHC Class I and Class II molecules differ not only in the origin of the antigens they present but also in their cellular distribution and the subsets of T cells they activate. This division of labor ensures a tailored immune response: cytotoxic T cells eliminate infected or malignant cells, while helper T cells coordinate broader immune activities, including B cell antibody production and macrophage activation [8],[9]. Dysregulation in MHC expression or antigen presentation pathways can contribute to immune evasion by pathogens and tumors or to the development of autoimmune diseases, where the immune system erroneously targets self-tissues. Advances in understanding MHC structure, antigen processing, and T cell recognition have informed the development of vaccines and immunotherapies [10]. For example, targeting MHC-presented epitopes has been key in designing peptide-based vaccines and cancer neoantigen therapies. Furthermore, MHC typing remains indispensable in transplant compatibility assessments and in predicting susceptibility to certain autoimmune disorders.

Conclusion

The Major Histocompatibility Complex is indispensable for effective immune surveillance and response, serving as the molecular interface between antigen processing and T cell-mediated immunity. Its dual role in presenting both endogenous and exogenous antigens ensures precise immune activation tailored to diverse threats. While MHC polymorphism enhances immune defense, it also complicates clinical interventions such as transplantation. Ongoing research into MHC function continues to reveal new insights with significant implications for immunology, vaccine development, and personalized medicine. Understanding and manipulating MHC-mediated antigen presentation holds promise for improving treatments against infectious diseases, cancer, and autoimmune conditions.

Acknowledgement

None

Conflict of Interest

None