Amino Acids

, Volume 46, Issue 5, pp 1265–1274 | Cite as

Decision-making critical amino acids: role in designing peptide vaccines for eliciting Th1 and Th2 immune response

  • Khurram Mushtaq
  • Sathi Babu Chodisetti
  • Pradeep K. Rai
  • Sudeep K. Maurya
  • Mohammed Amir
  • Javaid A. Sheikh
  • Javed N. Agrewala
Original Article


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.


Binding 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.

Supplementary material

726_2014_1692_MOESM1_ESM.tif (1022 kb)
Frequency of Th1 and Th2 skewing HLA binder peptides. Th1 (A) and Th2 (B) inducing peptides were checked for their binding capability with predominantly occurring HLA alleles in human population by using ProPred and SVMHC methods. Solid and open bars indicate binders and non-binders, respectively. X-axis represents the selected HLA alleles and Y-axis implies to the number of peptides. (TIFF 1021 kb)
726_2014_1692_MOESM2_ESM.tif (23 kb)
Incidence of Th1 and Th2 evoking HLA binding promiscuous peptides. Bar diagrams depict the percentage of Th1 and Th2 generating promiscuous and non-promiscuous peptides (A); strong and weak affinity binding Th1 and Th2 inducing promiscuous peptides (B). X-axis represents the type of peptides and Y-axis percentage of promiscuity (A); binding affinity (B). (TIFF 23 kb)
726_2014_1692_MOESM3_ESM.tif (53 kb)
Binding improves with increasing length of peptide. Solid and open bar diagrams illustrate strong and weak affinity of HLA-II binders, which activate Th1 (A) and Th2 (B) cells, respectively. X-axis represents the number of amino acids in each peptide, whereas Y-axis indicates the number of strong and weak binders. (TIFF 53 kb)
726_2014_1692_MOESM4_ESM.tif (52 kb)
Relationship between length of the peptide and its promiscuous nature. Solid and open bar diagrams depict promiscuous and non-promiscuous HLA-II binders that activate Th1 (A) and Th2 (B) cells, respectively. X-axis represents the number of amino acids in each peptide, whereas Y-axis indicates the number of promiscuous and non-promiscuous HLA-II peptide binders. (TIFF 51 kb)
726_2014_1692_MOESM5_ESM.tif (3.8 mb)
Conserved hydrophobicity of pTh1 and pTh2 observed with other MHC as well: Pie diagrams represent percentage of conserved hydrophobicity (black) and hydrophilicity (grey) at the indicated positions of peptide binding region that evoke Th1 (A); Th2 (B) response. Each bar graph represents percentage occurrence at the indicated position of binding region. X-axis represents the hydrophilicity in an increasing order and Y-axis denotes percentage of amino acid at the particular position. (TIFF 3850 kb)
726_2014_1692_MOESM6_ESM.tif (19.5 mb)
Distinct conformational binding of pTh1 and pTh2 and their consensus. Conformations of pTh1, pTh2 and their consensus sequence bound to HLA (A). The HLA molecule is shown in surface and peptides as stick representations. Arrow indicates binding groove of HLA. Peptide sequences of Fig. 3A are tabulated (B). (TIFF 19980 kb)
726_2014_1692_MOESM7_ESM.xlsx (64 kb)
List of total peptides used in the study: Excel file contains peptide sequences, source, organism and MHC restriction of used pTh1 and pTh2. (XLSX 63 kb)


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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Khurram Mushtaq
    • 1
  • Sathi Babu Chodisetti
    • 1
  • Pradeep K. Rai
    • 1
  • Sudeep K. Maurya
    • 1
  • Mohammed Amir
    • 1
  • Javaid A. Sheikh
    • 1
  • Javed N. Agrewala
    • 1
  1. 1.Immunology LaboratoryCSIR-Institute of Microbial TechnologyChandigarhIndia

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