Melanoma-associated antigen peptide-Major Histocompatibility Complex class I complex (TAA-MHC-I complex)

Melanoma-associated antigen (TAA) peptide-Major Histocompatibility Complex (MHC) class I complexes are the primary targets for cellular immunotherapies in melanoma. These complexes consist of short peptides derived from intracellular proteins—such as MART-1, gp100, or MAGE-A3—that are processed and loaded onto MHC class I molecules for surface display (Kawakami et al., 1994). Cytotoxic T-lymphocytes (CTLs) recognize these specific combinations via their T-cell receptors (TCRs), initiating a targeted immune attack against the malignant cell. Modern therapies like Tebentafusp (a bispecific TCR-anti-CD3 fusion) and Lifileucel (adoptive TIL therapy) specifically exploit these targets to treat advanced melanoma (Nathan et al., 2021; Rohaan et al., 2022). However, because many of these antigens are also expressed in normal melanocytes, treatment can lead to "on-target, off-tumor" toxicities such as vitiligo or uveitis. Furthermore, tumor resistance can occur through the downregulation of MHC expression or the loss of specific HLA alleles, which prevents CTL recognition (Garrido et al., 2016). Precision medicine approaches often require screening patients for specific HLA types, such as HLA-A*02:01, to ensure compatibility with the therapeutic TCR or bispecific agent.

Other names

Melanoma-associated antigensMHC-restricted tumor antigensHLA-peptide complexesMART-1/HLA-A2 complexgp100/HLA-A2 complexTumor-specific antigen peptides

Therapeutic agents recognize and bind the specific peptide-MHC complex on the melanoma cell surface, triggering the activation of cytotoxic T-lymphocytes (CTLs) and the subsequent lysis of the tumor cell through the release of cytotoxic proteins like perforin and granzymes.