What is the Difference Between HLA Class 1 and 2

The main difference between HLA class 1 and 2 is that HLA class 1 molecule presents antigens to cytotoxic T cells with CD8+ receptors whereas HLA class 2 molecule presents antigens to helper T cells with CD4+ receptors.

HLA  class 1 and 2 are two classes of HLA (Human Leukocyte antigen) molecules important as transplantation antigens. Their function is to present processed peptide antigens recognized by T cells. Moreover, the HLA region is the most polymorphic region in the human genome.

Key Areas Covered

1. What is HLA Class 1
   • Definition, Structure, Function
2. What is HLA Class 2
   • Definition, Structure, Function
3. Similarities Between HLA Class 1 and 2
   • Outline of Common Features
4. Difference Between HLA Class 1 and 2
   • Comparison with Key Differences

Key Terms

HLA Class 1, HLA Class 2, Transplantation

What is HLA Class 1

HLA class 1 is a class of HLA molecules that occurs on the surface of all nucleated cells in mammals. Structurally, it composes of three alpha domains (alpha 1, alpha 2, and alpha 3) and a single beta domain. Moreover, chromosome 6 encodes alpha domains, and chromosome 11encodes the beta domain. The alpha 3 domain serves as the membrane-spanning domain. In addition, alpha 1 and alpha 2 domains consist of the most variable amino acid sequences and peptide antigens bind to these two domains. HLA class 1 also contains three genes on chromosome 6: HLA-A, HLA-B, and HLA-C.

Figure 1: HLA Class 1

Furthermore, nucleated cells in the body express HLA class 1 molecules. These HLA molecules also present endogenous antigens that can be either self-proteins or foreign proteins including viral proteins, originating inside the cytoplasm. Upon presentation on the cell membrane, cytotoxic T cells recognize these antigens. However, killer T cells monitor these recognized antigens, destroying over-abundant or unfamiliar antigen-presenting cells.

What is HLA Class 2

HLA class 2 is another class of HLA molecules that occur on antigen-presenting cells such as macrophages, dendritic cells, and B cells.  These molecules consist of two alpha (alpha 1 and alpha 2) and two beta (beta 1 and beta 2) domains. However, both alpha and beta domains of the HLA class 2 molecules are encoded by chromosome 6. The alpha 2 and beta 2 domains serve as the membrane-spanning domains while alpha 1 and beta 1 domains serve as antigen-presenting domains.

Figure 2: HLA Class 2

Moreover, macrophages are the most professional phagocytes that engulf bacteria and virus-like foreign particles. Along with that, dendritic cells are a type of phagocytes that present antigens to T cells. In addition, B cells produce antibodies during humoral immunity. On the other hand, HLA class 2 molecules present exogenous antigens to helper T cells. Exogenous antigens originate extracellularly from bacteria-like foreign particles. In general,  phagocyted pathogens undergo degradation inside the antigen-presenting cells and peptide fragments occur on the cell membrane with the help of HLA class 2 molecules. More importantly, the recognized helper T cells undergo activation to release lymphokines, attracting other cells that destroy the antigenic material.

Similarities Between HLA Class 1 and 2

• HLA class 1 and 2 are two classes of human leukocyte antigens that occur on the surface of cells as cell receptors.
• Both consist of alpha and beta domains, presenting antigens to T cells to initiate immune responses.
• In addition, both are part of adaptive immunity, which is a type of specific immunity.

Difference Between HLA Class 1 and 2

Definition

HLA class 1 refers to a class of major histocompatibility complex molecules found on the surface of all nucleated cells in mammals while HLA class 2 refers to a class of major histocompatibility complex molecules mainly found on antigen-presenting cells such as macrophages, dendritic cells, and B cells.

Expression

Generally, HLA class 1 molecules are expressed on the cell membrane of all nucleated cells while HLA class 2 molecules are expressed on the surface of the antigen-presenting cells such as B cells, macrophages, and dendritic cells.  

Structure

HLA class 1 molecules consist of three alpha domains and a single beta domain while HLA class 2 molecules consist of two alpha and two beta domains.

Genes

In addition, the HLA class 1 domain consists of HLA-A, HLA-B, and HLA-C genes while the HLA class 2 domain consists of HLA-D genes.

Antigen Presentation

HLA class 1 molecules present endogenous antigens while HLA class 2 molecules present exogenous antigens.

Antigens Present to

Furthermore, the HLA class 1 molecule presents antigens to cytotoxic T cells with CD8+ receptors while the HLA class 2 molecule presents antigens to helper T cells with CD4+ receptors.

Conclusion

In brief, HLA class 1 and 2 are two types of antigen-presenting molecules that occur on the surface of different cells. HLA class 1 molecules present endogenous antigens to cytotoxic T cells while HLA class 2 molecules present antigens to helper T cells. In addition, HLA class 1 molecules occur on the cytoplasm of all nucleated cells and, HLA class 2 molecules occur on the cell membrane of the antigen-presenting cells. Therefore, the main difference between HLA class 1 and 2 molecules is their antigen presentation.

References:

1. Choo SY. The HLA system: genetics, immunology, clinical testing, and clinical implications. Yonsei Med J. 2007 Feb 28;48(1):11-23. doi: 10.3349/ymj.2007.48.1.11. PMID: 17326240; PMCID: PMC2628004.

Image Courtesy:

1. “MHC Class 1” By  atropos235- Own Work (CC BY 2.5) via Commons Wikimedia
2. “MHC Class 2” By  atropos235- Own Work (CC BY 2.5) via Commons Wikimedia