Resistance Associated Epitopes of HIV-1C – Highly Probable Candidates for a Multi-Epitope Vaccine

Jagadish Chandrabose Sundaramurthi, Soumya Swaminathan, and Luke Elizabeth Hanna

Journal Name: Immunogenetics (Springer)

Article type: Brief communications

Jagadish Chandrabose Sundaramurthi

Division of Biomedical Informatics,

Department of Clinical Research,

National Institute for Research in Tuberculosis

(Formerly Tuberculosis Research Centre), (ICMR),

Chennai, 600031, Tamil Nadu, India.

Soumya Swaminathan, and Luke Elizabeth Hanna

Division of HIV/AIDS,

Department of Clinical Research,

National Institute for Research in Tuberculosis

(Formerly Tuberculosis Research Centre), (ICMR),

Chennai, 600031, Tamil Nadu, India.

CORRESPONDING AUTHOR:

Dr.Luke Elizabeth Hanna

Scientist ‘C’

Division of HIV/AIDS,

Department of Clinical Research,

National Institute for Research in Tuberculosis,

(Formerly Tuberculosis Research Centre), Indian Council of Medical Research

1, Sathiyamoorthy Road

Chetpet, Chennai – 600 031

Tel.: +91 44 28369500

Fax: +91 44 28362528

E-mail address:

Supplementary information

Supplementary Figure 1: Schematic representation of work flow

Supplementary Table 1. List of CTL epitopes that selectively bind to HLA alleles associated with resistance or slow progression to HIV/AIDS.

S.
No. / Epitope / Protein / HXB2
start / Subtype / HLA
1 / HYMLKHIVW~ / p17 / 28 / A, C / A*2301
2 / HYMLNHIVW~ / p17 / 28 / A, C, D
3 / TLNAWVKVI$ / p24 / 19 / A, B, C, D / A*0201, A2
4 / VIYQYMDDL^ / RT / 179 / A, B, C,
CRF01_AE, D / A*0201, A2
5 / IAMESIVIW$ / RT / 375 / B, C / B*5703, B*58,
B*5801, B57
6 / THLEGKIIL$ / Integrase / 66 / B, C / B*1510, B15
7 / THLEGKVIL$ / Integrase / 66 / C / B*1510
8 / FPRPWLHSL$ / Vpr / 34 / C
9 / RILQQLLFI$ / Vpr / 62 / A, B, C, D, M / A*0201, A2,
A2 supertype
10 / WYIKIFIII$ / gp160 / 680 / AE, B, C
11 / WYIRIFIMI$ / gp160 / 680 / C
12 / VSGFLALAW / gp160 / 749 / A, B, C, D
13 / GALDLSHFL$ / Nef / 83 / A1, AG, B, C / A2
14 / AAFDLSFFL$ / Nef / 83 / C / B*5703
15 / QDILDLWIY~ / Nef / 107 / B, C / B18
16 / LTFGWCFKL$ / Nef / 136 / A, B, C / A*0201, A2,
A2 supertype,
B*1517, B57, B63

All of the 16 epitopes listed were predicted as strong binders to all three HLA alleles by MODPROPEP. Of these, 11 epitopes($)were identified as binders to all three HLA alleles, 1 epitope(^) as binder to HLA-A*0201 and HLA-B*5101, and 3 epitopes(~) as binders to HLA-B*2705 and HLA-B*5101, and 1 epitope (S. No. 12) as binder to HLA-B*5101 using the second method (IEDB consensus method). Collectively, 15 epitopes were identified by both methods as strong binders to at least two or all three resistant associated HLA alleles.

Supplementary Figure 2: Interaction profile of HLA-A*0201 and Epitopep17 (77-85 SLFNTVATL); the binding energy of this epitope with HLA-A*0201was -51.4 kcal/mol against the-46.16 kcal/molof peptide-HLA-A*0201complex present in 1I1Y.

Supplementary Figure 3:Interaction profile of HLA-B*B2705 and Epitopep17 (77-85 SLFNTVATL); the binding energy of this epitope with HLA-B*B2705was - 45.28 kcal/mol against the -39.01 kcal/mol of peptide- HLA-B*B2705 complex present in 1OGT.

Supplementary Figure 4: Interaction profile of HLA-B* 5101 and Epitope p17 (77-85 SLFNTVATL); the binding energy of this epitope with HLA-B* 5101was - 64.58 kcal/mol against the - 60.48 kcal/mol of peptide-HLA-B* 5101complex present in 1E27.

Supplementary Figure 5: Electrostatic potential of HLA-A*0201 and effective fitting of the Epitope onto the groove of the HLA.

Supplementary Table 2. Interaction profile of p17 (77-85SLFNTVATL) with 3 HLA alleles studied.

Epitope Residue HLA-A*0201HLA-B*2705HLA-B*5101

epitope atom-HLA residue:number:atom(distance)

E1SN -TYR:7:OH (2.6)N-TYR:7:OH (2.6)O-TYR:159:OH (2.7)

O-TYR:159:OH (2.8)O-TYR:159:OH (2.8)

N-TYR:171:OH (2.7)N-TYR:171:OH (2.7)

E2LN-GLU:63 OE1 (4)O-ARG:62:NH1-

(3.2)

O-LYS:66NZ (2.6)N-GLU:63 OE2

(3)

E3FN-TYR:99:OH(3.2)N-TYP:99:OH(3)O-TYR:9:OH (3)

E4N---

E5T--O-THR:73:OG1(2.8)

OG1-TYR:99:OH (3)

E6VO-THR:73:OG1 (3)--

E7A---

E8TO-TRP:147:NE1 (2.8)O-TRP:147:NE1(2.9)O-TRP:147:NE1 (3)

E9LN-ASP:77:OD1(3)N-ASP:77:OD1(3.1)N-ASN:77:OD1 (2.9)

O-LYS146:NZ(2.8)O-LYS:146:NZ(2.8)O-TYR:84:OH (2.9)

O-THR:143:OG1 (2.5)