Decision-making critical amino acids: role in designing peptide vaccines for eliciting Th1 and Th2 immune response
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CD4 T cells play a cardinal role in orchestrating immune system. Differentiation of CD4 T cells to Th1 and Th2 effector subsets depends on multiple factors such as relative intensity of interactions between T cell receptor with peptide-major histocompatibility complex, cytokine milieu, antigen dose, and costimulatory molecules. Literature supports the critical role of peptide’s binding affinity to Human Leukocyte Antigens (HLAs) and in the differentiation of naïve CD4 T cells to Th1 and Th2 subsets. However, there exists no definite report addressing very precisely the correlation between physicochemical properties (hydrophobicity, hydrophilicity), pattern, position of amino acids in peptide and their role in skewing immune response towards Th1 and Th2 cells. This may play a significant role in designing peptide vaccines. Hence in the present study, we have evaluated the relationship between amino acid pattern and their influence in differentiation of Th1 and Th2 cells. We have used a data set of 320 peptides, whose role has been already established experimentally in the generation of either Th1 or Th2 immune response. Further, characterization was done based on binding affinity, promiscuity, amino acid pattern and binding conformation of peptides. We have observed that distinct amino acids in peptides elicit either Th1 or Th2 immunity. Consequently, this study signifies that alteration in the sequence and type of selected amino acids in the HLA class II binding peptides can modulate the differentiation of Th1 and Th2 cells. Therefore, this study may have an important implication in providing a platform for designing peptide-based vaccine candidates that can trigger desired Th1 or Th2 response.
KeywordsBinding affinity Multiple sequence alignment Promiscuous peptides Th1 and Th2 immune response
Human leukocyte antigen
Multiple sequence alignment
- pTh1 and pTh2
Peptides eliciting Th1 and Th2 immune response, respectively
The authors are thankful to Dr. Balvinder Singh, CSIR-Institute of Microbial Technology, Chandigarh for valuable suggestions and Dr. Uthaman Gowthaman, Yale School of Medicine, New Haven, USA for peptide data collection. The authors also thank Council of Scientific and Industrial Research (CSIR), India for financial support. SBC, KM, PKR, SM, JAS are recipients of fellowship of CSIR, and MA of UGC.
Conflict of interest
The authors have no financial conflict of interest.
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