Major Histocompatibility Complex class I and II molecules presenting SARS-CoV-2 spike-derived peptides (MHC-I/II-S)

The Major Histocompatibility Complex (MHC) class I and II molecules presenting SARS-CoV-2 spike-derived peptides are the fundamental targets for T-cell-mediated immunity against COVID-19 (Grifoni et al., 2020). MHC class I molecules display endogenous spike fragments to CD8+ T cells to facilitate the clearance of infected cells, while MHC class II molecules present exogenous fragments to CD4+ T cells to drive B-cell maturation and cytokine production (Sette & Crotty, 2021). This complex is the functional endpoint of most COVID-19 vaccines, including mRNA-based (BNT162b2, mRNA-1273) and viral vector-based (AZD1222) platforms, which rely on the host's antigen presentation machinery to prime the adaptive immune system (Sahin et al., 2021). The efficacy of these vaccines is heavily dependent on the binding affinity of spike peptides to a patient's specific HLA alleles, making HLA polymorphism a critical factor in population-wide immunity (StatPearls, 2023). Beyond vaccines, these complexes are targets for emerging immunotherapies, such as TCR-engineered T cells and TCR-like antibodies designed to recognize specific viral epitopes. Safety considerations include the risk of molecular mimicry, where spike peptides might resemble self-antigens, potentially leading to autoimmune complications. Monitoring these complexes via ELISpot assays or MHC-peptide multimers is essential for evaluating the longevity and breadth of the immune response against emerging viral variants.

Other names

HLA-spike peptide complexSARS-CoV-2 spike epitope-MHC complexpMHC complexMHC-S peptide complexMajor Histocompatibility Complex presenting spike-derived peptides

Presentation of viral epitopes to T-cell receptors (TCRs) to activate CD4+ and CD8+ T-cell mediated immunity.