If the problem is that your son has different interests than the other children in his class, help him find some groups to join that share the same interests. Joining a soccer team, a Boy Scout troop, or a computer club could help your son make friends with children with similar interests to his own.
Talk with the school counselor about the self-esteem issue. She may be able to give your son some individual time or include him in a small group. If you decide to get additional help outside the school, the counselor or your pediatrician can refer you to a therapist in your community.